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All's well that ends well
(2009)
A few years ago, Jasanoff adopted the central tenet of my accentological theory, viz. that the Balto-Slavic acute was a stød or glottal stop, not a rising tone (cf. Kortlandt 1975, 1977, 2004, Jasanoff 2004a). Of course, nobody will believe Jasanoff’s claim that he arrived at the same result independently thirty years after I published it and ten years after we discussed it when he came to Leiden to visit us. Though at the time he haughtily dismissed “the tangle of secondary hypotheses and “laws” that clutter the ground in the field of Balto-Slavic accentology” (Jasanoff 2004b: 171), he has now recognized the importance of Pedersen’s law, Hirt’s law, Winter’s law, Meillet’s law, Dolobko’s law, Dybo’s law and Stang’s law and largely accepted my relative chronology of these accent laws, including the loss of the acute shortly before Stang’s law (cf. Jasanoff 2008). He has also accepted my split of Pedersen’s law into a Balto-Slavic and a Slavic phase (to which a Lithuanian phase must be added), my thesis that the tonal contours of Baltic and Slavic languages are post-Balto-Slavic innovations (cf. Jasanoff 2008: 344, fn. 10), and the rise of a tonal distinction on non-acute initial syllables before Dybo’s law which I discussed at some length in my review (1978) of Garde’s monograph (1976). This is great progress.
The current thesis is devoted to a systematic study of fluctuations and correlations in heavy-ion collisions, which might be considered as probes for the phase transition and the critical point in the phase diagram, within the Hadron-String- Dynamics (HSD) microscopic transport approach. This is a powerful tool to study nucleus-nucleus collisions and allows to completely simulate experimental collisions on an event-by-event basis. Thus, the transport model has been used to study fluctuations and correlations including the influence of experimental acceptance as well as centrality, system size and collision energy. The comparison to experimental data can separate the effects induced by a phase transition since there is no phase transition in the HSD version used here. Firstly the centrality dependence of multiplicity fluctuations has been studied. Different centrality selections have been performed in the analysis in correspondence to the experimental situation. For the fixed target experiment NA49 events with fixed numbers of the projectile participants have been studied while in the collider experiment PHENIX centrality classes of events have been defined by the multiplicity in certain phase space region. A decrease of participant number fluctuations (and thus volume fluctuations) in more central collisions for both experiments has been obtained. Another area of this work addresses to transport model calculations of multiplicity fluctuations in nucleus-nucleus collisions as a function of colliding energy and system size. This study is in full correspondence to the experimental program of the NA61 Collaboration at the SPS. Central C+C, S+S, In+In, and Pb+Pb nuclear collisions at Elab = 10, 20, 30, 40, 80, 158 AGeV have been investigated. The expected enhanced fluctuations - attributed to the critical point and phase transition - can be observed experimentally on top of a monotonic and smooth ‘hadronic background’. These findings should be helpful for the optimal choice of collision systems and collision energies for the experimental search of the QCD critical point. Other observables are fluctuations of ratios of hadrons (e.g. pions, kaons, protons, etc.) which are not so much affected by volume fluctuations. In particular HSD results for the kaon-to-pion ratio fluctuations, which has been regarded as promising observable for a long time, are presented from low SPS energies up to high energies at RHIC. In addition to the HSD calculations statistical model is also used in terms of microcanonical, canonical and grand canonical ensembles. Further a study of the system size event-by-event fluctuations causing rapidity forward-backward correlations in relativistic heavy-ion collisions is presented. The HSD simulations reveal strong forward-backward correlations and reproduce the main qualitative features of the STAR data in A+A collisions at RHIC energies. It has been shown that strong forward-backward correlations arise due to an averaging over many different events that belong to one centrality bin. An optimization of the experimental selection of centrality classes is presented, which is relevant for the program of the NA61 collaboration at CERN, the low-energy program at RHIC, as well as future experiments at FAIR.
Ein wesentliches Ziel der Physik mit schweren Ionen ist die Untersuchung der Zustände von Kernmaterie bei hohen Dichten bzw. Temperaturen. Solche Zustände lassen sich durch Kollisionen von hochenergetischen schweren Ionen in Teilchenbeschleunigern wie dem Super Proton Synchrotron SPS am Europäischen Kernforschungszentrum CERN in Genf erzeugen und untersuchen. Die vorliegende Arbeit beschäftigt sich mit der Analyse des Einflusses des in einer solchen Kollision erzeugten Mediums auf hochenergetische Teilchen, welche dieses Medium durchqueren. Hierzu werden Korrelationen zwischen Teilchen mit hohem Transversalimpuls pt als Funktion der Zentralität der Kollisionen und der Ladung der beteiligten Teilchen untersucht. Ziel ist es, hierdurch eine experimentelle Grundlage für die theoretische Beschreibung der Eigenschaften des Mediums in solchen Kollisionen bereitzustellen. ...
Kaon and pion production in centrality selected minimum bias Pb+Pb collisions at 40 and 158A GeV
(2009)
Results on charged kaon and negatively charged pion production and spectra for centrality selected Pb+Pb mininimum bias events at 40 and 158A GeV have been presented in this thesis. All analysis are based on data taken by the NA49 experiment at the accelerator Super Proton Synchrotron (SPS) at the European Organization for Nuclear Research (CERN) in Geneva, Switzerland. The kaon results are based on an analysis of the mean energy loss <dE/dx> of the charged particles traversing the detector gas of the time projection chambers (TPCs). The pion results are from an analysis of all negatively charged particles h- corrected for contributions from particle decays and secondary interactions. For the dE/dx analysis of charged kaons, main TPC tracks with a total momentum between 4 and 50 GeV have been analyzed in logarithmic momentum log(p) and transverse momentum pt bins. The resulting dE/dx spectra have been fitted by the sum of 5 Gaussians, one for each main particle type (electrons, pions, kaons, protons, deuterons). The amplitude of the Gaussian used for the kaon part of the spectra has been corrected for efficiency and acceptance and the binning has been transformed to rapidity y and transverse momentum pt bins. The multiplicity dN/dy of the single rapidity bins has been derived by summing the measured range of the transverse momentum spectra and an extrapolation to full coverage with a single exponential function fitted to the measured range. The results have been combined with the mid-rapidity measurements from the time-of-flight detectors and a double Gaussian fit to the dN/dy spectra has been used for extrapolation to rapidity outside of the acceptance of the dE/dx analysis. For the h- analysis of negatively charged pions, all negatively charged tracks have been analyzed. The background from secondary reactions, particle decays, and gamma-conversions has been corrected with the VENUS event generator. The results were also corrected for efficiency and acceptance and the pt spectra were analyzed and extrapolated where necessary to derive the mean yield per rapidity bin dN/dy. The mean multiplicity <pi-> has been derived by summing up the measured dN/dy and extrapolating the rapidity spectrum with a double Gaussian fit to 4pi coverage. The results have been discussed in detail and compared to various model calculations. Microscopical models like URQMD and HSD do not describe the full complexity of Pb+Pb collisions. Especially the production of the positively charged kaons, which carry the major part of strange quarks, cannot be consistently reproduced by the model calculations. Centrality selected minimum bias Pb+Pb collisions can be described as a mixture of a high-density region of multiply colliding nucleons (core) and practically independent nucleon-nucleon collisions (corona). This leads to a smooth evolution from peripheral to central collisions. A more detailed approach derives the ensemble volume from a percolation of elementary clusters. In the percolation model all clusters are formed from coalescing strings that are assumed to decay statistically with the volume dependence of canonical strangeness suppression. The percolation model describes the measured data for top SPS and RHIC energies. At 40A GeV, the system size dependence of the relative strangeness production starts to evolve from the saturation seen at higher energies from peripheral events onwards towards a linear dependence at SIS and AGS. This change of the dependence on system size occurs in the energy region of the observed maximum of the K+ to pi ratio for central Pb+Pb collisions. Future measurements with heavy ion beam energies around this maximum at RHIC and FAIR as well as the upgraded NA49 successor experiment NA61 will further improve our understanding of quark matter and its reflection in modern heavy ion physics and theories.
The likely manifestations of climate change like flood hazards are prominent topics in public communication. This can be shown by media analysis and questionnaire data. However, in the case of flood risks an information gap remains resulting in misinformed citizens who probably will not perform the necessary protective actions when an emergency occurs. This paper examines more closely a newly developed approach to flood risk communication that takes the heterogeneity of citizens into account and aims to close this gap. The heterogeneity is analysed on the meso level regarding differences in residential situation as well as on the micro level with respect to risk perception and protective actions. Using the city of Bremen as a case study, empirical data from n=831 respondents were used to identify Action Types representing different states of readiness for protective actions in view of flood risks. These subpopulations can be provided with specific information to meet their heterogeneous needs for risk communication. A prototype of a computer-based information system is described that can produce and pass on such tailored information. However, such an approach to risk communication has to be complemented by meso level analysis which takes the social diversity of subpopulations into account. Social vulnerability is the crucial concept for understanding the distribution of resources and capacities among different social groups. We therefore recommend putting forums and organisations into place that can mediate between the state and its citizens.
Background Ongoing changes in cancer care cause an increase in the complexity of cases which is characterized by modern treatment techniques and a higher demand for patient information about the underlying disease and therapeutic options. At the same time, the restructuring of health services and reduced funding have led to the downsizing of hospital care services. These trends strongly influence the workplace environment and are a potential source of stress and burnout among professionals working in radiotherapy. Methods and patients A postal survey was sent to members of the workgroup "Quality of Life" which is part of DEGRO (German Society for Radiooncology). Thus far, 11 departments have answered the survey. 406 (76.1%) out of 534 cancer care workers (23% physicians, 35% radiographers, 31% nurses, 11% physicists) from 8 university hospitals and 3 general hospitals completed the FBAS form (Stress Questionnaire of Physicians and Nurses; 42 items, 7 scales), and a self-designed questionnaire regarding work situation and one question on global job satisfaction. Furthermore, the participants could make voluntary suggestions about how to improve their situation. Results Nurses and physicians showed the highest level of job stress (total score 2.2 and 2.1). The greatest source of job stress (physicians, nurses and radiographers) stemmed from structural conditions (e.g. underpayment, ringing of the telephone) a "stress by compassion" (e.g. "long suffering of patients", "patients will be kept alive using all available resources against the conviction of staff"). In multivariate analyses professional group (p < 0.001), working night shifts (p = 0.001), age group (p = 0.012) and free time compensation (p = 0.024) gained significance for total FBAS score. Global job satisfaction was 4.1 on a 9-point scale (from 1 – very satisfied to 9 – not satisfied). Comparing the total stress scores of the hospitals and job groups we found significant differences in nurses (p = 0.005) and physicists (p = 0.042) and a borderline significance in physicians (p = 0.052). In multivariate analyses "professional group" (p = 0.006) and "vocational experience" (p = 0.036) were associated with job satisfaction (cancer care workers with < 2 years of vocational experience having a higher global job satisfaction). The total FBAS score correlated with job satisfaction (Spearman-Rho = 0.40; p < 0.001). Conclusion Current workplace environments have a negative impact on stress levels and the satisfaction of radiotherapy staff. Identification and removal of the above-mentioned critical points requires various changes which should lead to the reduction of stress.
We calculate leading-order dilepton yields from a quark-gluon plasma which has a time-dependent anisotropy in momentum space. Such anisotropies can arise during the earliest stages of quark-gluon plasma evolution due to the rapid longitudinal expansion of the created matter. A phenomenological model for the proper time dependence of the parton hard momentum scale, p_hard, and the plasma anisotropy parameter, xi, is proposed. The model describes the transition of the plasma from a 0+1 dimensional collisionally-broadened expansion at early times to a 0+1 dimensional ideal hydrodynamic expansion at late times. We find that high-energy dilepton production is enhanced by pre-equilibrium emission up to 50% at LHC energies, if one assumes an isotropization/thermalization time of 2 fm/c. Given sufficiently precise experimental data this enhancement could be used to determine the plasma isotropization time experimentally.
Background Hepatitis C virus (HCV) is a leading cause of chronic liver disease, end-stage cirrhosis, and liver cancer, but little is known about the burden of disease caused by the virus. We summarised burden of disease data presently available for Europe, compared the data to current expert estimates, and identified areas in which better data are needed. Methods Literature and international health databases were systematically searched for HCV-specific burden of disease data, including incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and liver transplantation. Data were collected for the WHO European region with emphasis on 22 countries. If HCV-specific data were unavailable, these were calculated via HCV-attributable fractions. Results HCV-specific burden of disease data for Europe are scarce. Incidence data provided by national surveillance are not fully comparable and need to be standardised. HCV prevalence data are often inconclusive. According to available data, an estimated 7.3–8.8 million people (1.1–1.3%) are infected in our 22 focus countries. HCV-specific mortality, DALY, and transplantation data are unavailable. Estimations via HCV-attributable fractions indicate that HCV caused more than 86000 deaths and 1.2 million DALYs in the WHO European region in 2002. Most of the DALYs (95%) were accumulated by patients in preventable disease stages. About one-quarter of the liver transplants performed in 25 European countries in 2004 were attributable to HCV. Conclusion Our results indicate that hepatitis C is a major health problem and highlight the importance of timely antiviral treatment. However, data on the burden of disease of hepatitis C in Europe are scarce, outdated or inconclusive, which indicates that hepatitis C is still a neglected disease in many countries. What is needed are public awareness, co-ordinated action plans, and better data. European physicians should be aware that many infections are still undetected, provide timely testing and antiviral treatment, and avoid iatrogenic transmission.
This thesis contributes to the field of soft matter research and studies the importance of hydrodynamic interactions during free-solution electrophoresis of linear polyelectrolytes by means of coarse-grained molecular dynamics simulations including full electro-hydrodynamic interactions. The center of attention is the specific role of hydrodynamic interactions on the electrophoretic behaviour of charged macromolecules. Points of interest are the dependence of hydrodynamic interactions on the chain length, the chain flexibility and the surrounding counterions, and their combined influence on important observables such as the static chain conformations and the dynamic transport coefficients, i.e., the diffusion and the electrophoretic mobility. These problems are addressed by extensive computer simulations that are quantitatively matched with experimental results. Existing theoretical predictions are carefully examined and are augmented by the observations in this thesis.
Stocks are exposed to the risk of sudden downward jumps. Additionally, a crash in one stock (or index) can increase the risk of crashes in other stocks (or indices). Our paper explicitly takes this contagion risk into account and studies its impact on the portfolio decision of a CRRA investor both in complete and in incomplete market settings. We find that the investor significantly adjusts his portfolio when contagion is more likely to occur. Capturing the time dimension of contagion, i.e. the time span between jumps in two stocks or stock indices, is thus of first-order importance when analyzing portfolio decisions. Investors ignoring contagion completely or accounting for contagion while ignoring its time dimension suffer large and economically significant utility losses. These losses are larger in complete than in incomplete markets, and the investor might be better off if he does not trade derivatives. Furthermore, we emphasize that the risk of contagion has a crucial impact on investors' security demands, since it reduces their ability to diversify their portfolios.
Molecules of the title compound, C40H42BrNO6, are located on a crystallographic twofold rotation axis. As a result, the nitro group and bromine residue are mutually disordered with equal occupancies. The propoxy-substituted aromatic rings are close to parallel to each other [dihedral angle = 21.24 (1)°], whereas the propenoxy-substituted rings enclose a dihedral angle of 70.44 (1)°. The dihedral angles between the methylene C atoms and the aromatic rings shows that the propenoxy substituted rings are bent away from the calixarene cavity [dihedral angle between the planes = 35.22 (8)°], whereas the propoxy-substituted rings are almost perpendicular [79.38 (10)°] to the plane of the methylene C atoms. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.006 A° ; disorder in main residue; R factor = 0.065; wR factor = 0.130; data-to-parameter ratio = 11.8.
The title compound, C14H9Cl3N2OS, has bond lengths and angles which are quite typical for thiourea compounds of this class. The molecule exists in the solid state in its thione form with typical thiourea C=S and C=O bond lengths, as well as shortened C-N bonds. An intramolecular N-H...O hydrogen bond stabilizes the molecular conformation. Intermolecular N-H...S hydrogen bonds link the molecules to form centrosymmetric dimers. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.002 A° ; R factor = 0.029; wR factor = 0.078; data-to-parameter ratio = 17.2.
The title compound, C22H18N2O2, was derived from 1-(2-hydroxyphenyl)-3-(4-methoxyphenyl)propane-1,3-dione. The central pyrazole ring forms dihedral angles of 16.83 (5), 48.97 (4) and 51.68 (4)°, respectively, with the methoxyphenyl, phenyl and hydroxyphenyl rings. The crystal packing is stabilized by O-H...N hydrogen bonding. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.002 Å; R factor = 0.037; wR factor = 0.096; data-to-parameter ratio = 17.0.
The title molecule, C14H9ClN2OS, exists in the solid state in its amide form with a typical C=O bond length, as well as shortened C-N bonds. The plane containing the HNCO atoms subtends dihedral angles of 12.3 (4) and 8.1 (3)° with the planes of the phenyl ring and benzothiazole group, respectively, whereas the dihedral angle between the planes of the phenyl ring and the benzothiazole group is 5.96 (6)°. In the crystal, molecules form intermolecular N-H...N hydrogen bonds, generating independent scissor-like R22(8) dimers. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.002 Å; R factor = 0.028; wR factor = 0.079; data-to-parameter ratio = 13.3.
In the title compound, C15H17ClN2O4S, the atoms in the hydantoin ring are coplanar (r.m.s. deviation = 0.006 Å). The crystal structure is stabilized by intermolecular N-H...O hydrogen bonds which link the molecules into centrosymmetric dimers. The dihedral angle subtended by the 4-chlorophenyl group with the plane passing through the hydantoin unit is 82.98 (4)°. The cyclohexyl ring adopts an ideal chair conformation. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.002 Å; R factor = 0.030; wR factor = 0.081; data-to-parameter ratio = 15.0.
In the title Grignard reagent, [MgBr(C12H9)(C5H10O)2], the Mg centre adopts a distorted tetrahedral MgCO2Br arrangement. The dihedral angle between the two aromatic rings of the biphenyl residue is 44.00 (14)°. Each molecule incorporates one R- and one S-configured 2-methyltetrahydrofuran molecule. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.007 Å; R factor = 0.045; wR factor = 0.108; data-to-parameter ratio = 17.4.
The two aromatic rings in the title compound, C15H12Cl2N2O2S, enclose a dihedral angle of 37.49 (6)°. The molecule exists in the solid state in its thione form with typical thiourea C-S and C-O bonds lengths, as well as shortened C-N bonds. An intramolecular N-H...O hydrogen bond stabilizes the molecular conformation. In the crystal, molecules are connected by N-H...O and N-H...S hydrogen bonds, forming chains running along the alpha axis. Key indicators: single-crystal X-ray study; T = 173 K; mean σ (C–C) = 0.002 Å; disorder in main residue; R factor = 0.035; wR factor = 0.087; data-to-parameter ratio = 18.9.
The asymmetric unit of the title compound, C14H8Cl4N2OS·0.5H2O, contains two independent molecules with different conformations with respect to the aromatic ring planes, and one water molecule. The bond lengths and angles are typical of thiourea compounds of this class. The molecule exists in the solid state in its thione form with typical thiourea C-S and C-O bonds lengths, as well as shortened C-N bonds. The dihedral angles between the two aromatic planes are 66.93 (8) and 60.44 (9)° in the two independent molecules. An intramolecular N-H...O hydrogen bond stabilizes the molecular conformation and the crystal packing is characterized by N-H...O, O-H...S and O-H...Cl hydrogen bonds. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.004 Å; R factor = 0.045; wR factor = 0.125; data-to-parameter ratio = 16.8.
The crystal structure of the title compound, C14H8Cl4N2OS, is composed of discrete molecules with bond lengths and angles quite typical for thiourea compounds of this class. The plane containing the central SONNCC atom set subtends a dihedral angle of 31.47 (3)° with the benzene ring. An intramolecular N-H...O hydrogen bond stabilizes the molecular conformation and the molecules form centrosymmetric dimers via intermolecular N-H...S hydrogen bonds. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.002 Å; R factor = 0.032; wR factor = 0.087; data-to-parameter ratio = 17.9.
The title compound, C14H6Cl6N2OS·0.5CHCl3, crystallizes with four 1-(2,6-dichlorobenzoyl)-3- (2,3,5,6-tetrachlorophenyl)thiourea molecules and two trichloromethane molecules in the asymmetric unit. The thiourea molecules exist in the solid state in their thione forms with typical thiourea C-S and C-O bonds lengths, as well as shortened C-N bonds. The -NH-C(=S)-NH-C(=O)- plane is almost perpendicular to the benzene ring in each thiourea molecule. Intramolecular N-H...O hydrogen bonds stabilize the molecular conformation and intermolecular N-H...S hydrogen bonds stabilize the packing arrangement. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.004 Å; R factor = 0.051; wR factor = 0.147; data-to-parameter ratio = 23.2.
The structure of the title compound, C14H9Cl3N2OS, is composed of discrete molecules with bond lengths and angles quite typical for thiourea compounds of this class. The plane containing the thiocarbonyl and carbonyl groups subtends dihedral angles of 48.19 (3) and 87.51 (3)° with the planes formed by the 3-chloro and 2,6-dichlorophenyl rings, respectively; the dihedral angle between the two benzene ring planes is 45.32 (3)°. An intramolecular N-H...O hydrogen bond stabilizes the molecular conformation and the molecules form intermolecular N-H...S and N-H...O hydrogen bonds, generating a sheet along the alpha axis. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.002 Å; R factor = 0.037; wR factor = 0.094; data-to-parameter ratio = 25.5.
The title molecule, C16H15ClN2OS, exists in the solid state in its thione form with typical thiourea C-S and C-O bonds lengths, as well as shortened C-N bonds. An intramolecular N-H...O hydrogen bond stabilizes the molecular conformation and intermolecular N-H...S hydrogen bonds link the molecules into centrosymmetric dimers. The dihedral angle between the aromatic rings is 50.18 (5)°. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.002 Å; R factor = 0.032; wR factor = 0.085; data-to-parameter ratio = 15.3.
The crystal structure of the title compound, C15H17BrN2O4S, is stabilized by intermolecular N-H...O hydrogen bonds which link the molecules into centrosymmetric dimers. The dihedral angle subtended by the 4-bromophenyl group with the mean plane passing through the hydantoin unit is 83.29 (5)°. The cyclohexyl group adopts an ideal chair conformation with the methyl group in an equatorial position. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.003 Å; R factor = 0.030; wR factor = 0.070; data-to-parameter ratio = 16.8.
The title compound, Cs2Mg(H2P2O7)2·2H2O, is isostructural with the related known isoformular phosphates. The crystal framework consists of corner-sharing MgO6 and H2P2O7 polyhedra, leading to tunnels parallel to the b-axis direction in which Cs+ ions are located. The H2P2O7 unit shows a bent eclipsed conformation. The Mg2+ ion lies on an inversion center. The water molecules form hydrogen bonds to O atoms of two different dihydrogenphosphate ions, which are further hydrogen bonded to symmetry-equivalent dihydrogenphosphate ions. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(P–O) = 0.006 Å; R factor = 0.048; wR factor = 0.125; data-to-parameter ratio = 12.3.
In the title molecule, C13H16ClNO, the mean plane of the atoms in the -CONH- group forms a dihedral angle of 42.0 (4)° with the benzene ring plane. In the crystal structure, molecules are linked by intermolecular N-H...O hydrogen bonds, generating C(4) chains along [100]. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.002 Å; R factor = 0.030; wR factor = 0.069; data-to-parameter ratio = 18.2.
Diffusion of inner membrane proteins is a prerequisite for correct functionality of mitochondria. The complicated structure of tubular, vesicular or flat cristae and their small connections to the inner boundary membrane impose constraints on the mobility of proteins making their diffusion a very complicated process. Therefore we investigate the molecular transport along the main mitochondrial axis using highly accurate computational methods. Diffusion is modeled on a curvilinear surface reproducing the shape of mitochondrial inner membrane (IM). Monte Carlo simulations are carried out for topologies resembling both tubular and lamellar cristae, for a range of physiologically viable crista sizes and densities. Geometrical confinement induces up to several-fold reduction in apparent mobility. IM surface curvature per se generates transient anomalous diffusion (TAD), while finite and stable values of projected diffusion coefficients are recovered in a quasi-normal regime for short- and long-time limits. In both these cases, a simple area-scaling law is found sufficient to explain limiting diffusion coefficients for permeable cristae junctions, while asymmetric reduction of the junction permeability leads to strong but predictable variations in molecular motion rate. A geometry-based model is given as an illustration for the time-dependence of diffusivity when IM has tubular topology. Implications for experimental observations of diffusion along mitochondria using methods of optical microscopy are drawn out: a non-homogenous power law is proposed as a suitable approach to TAD. The data demonstrate that if not taken into account appropriately, geometrical effects lead to significant misinterpretation of molecular mobility measurements in cellular curvilinear membranes.
Poster presentation: An important challenge in neuroscience is understanding how networks of neurons go about processing information. Synapses are thought to play an essential role in cellular information processing however quantitative and mathematical models of the underlying physiologic processes that occur at synaptic active zones are lacking. We are generating mathematical models of synaptic vesicle dynamics at a well-characterized model synapse, the Drosophila larval neuromuscular junction. This synapse's simplicity, accessibility to various electrophysiological recording and imaging techniques, and the genetic malleability intrinsic to Drosophila system make it ideal for computational and mathematical studies. We have employed a reductionist approach and started by modeling single presynaptic boutons. Synaptic vesicles can be divided into different pools; however, a quantitative understanding of their dynamics at the Drosophila neuromuscular junction is lacking [4]. We performed biologically realistic simulations of high and low release probability boutons [3] using partial differential equations (PDE) taking into account not only the evolution in time but also the spatial structure in two dimensions (the extension to three dimensions will be implemented soon). PDEs are solved using UG, a program library for the calculation of multi-dimensional PDEs solved using a finite volume approach and implicit time stepping methods leading to extended linear equation systems be solvedwith multi-grid methods [3,4]. Numerical calculations are done on multi-processor computers for fast calculations using different parameters in order to asses the biological feasibility of different models. In preliminary simulations, we modeled vesicle dynamics as a diffusion process describing exocytosis as Neumann streams at synaptic active zones. The initial results obtained with these models are consistent with experimental data. However, this should be regarded as a work in progress. Further refinements will be implemented, including simulations using morphologically realistic geometries which were generated from confocal scans of the neuromuscular junction using NeuRA (a Neuron Reconstruction Algorithm). Other parameters such as glutamate diffusion and reuptake dynamics, as well as postsynaptic receptor kinetics will be incorporated as well.
Poster presentation: Our work deals with the self-organization [1] of a memory structure that includes multiple hierarchical levels with massive recurrent communication within and between them. Such structure has to provide a representational basis for the relevant objects to be stored and recalled in a rapid and efficient way. Assuming that the object patterns consist of many spatially distributed local features, a problem of parts-based learning is posed. We speculate on the neural mechanisms governing the process of the structure formation and demonstrate their functionality on the task of human face recognition. The model we propose is based on two consecutive layers of distributed cortical modules, which in turn contain subunits receiving common afferents and bounded by common lateral inhibition (Figure 1). In the initial state, the connectivity between and within the layers is homogeneous, all types of synapses – bottom-up, lateral and top-down – being plastic. During the iterative learning, the lower layer of the system is exposed to the Gabor filter banks extracted from local points on the face images. Facing an unsupervised learning problem, the system is able to develop synaptic structure capturing local features and their relations on the lower level, as well as the global identity of the person at the higher level of processing, improving gradually its recognition performance with learning time. ...
Poster presentation: Introduction We study the problem of object recognition invariant to transformations, such as translation, rotation and scale. A system is underdetermined if its degrees of freedom (number of possible transformations and potential objects) exceed the available information (image size). The regularization theory solves this problem by adding constraints [1]. It is unclear what constraints biological systems use. We suggest that rather than seeking constraints, an underdetermined system can make decisions based on available information by grouping its variables. We propose a dynamical system as a minimum system for invariant recognition to demonstrate this strategy. ...
Central America is one of the world’s most herpetological diverse areas in relation to its size. Nicaragua is the largest country in this region and separates Nuclear from Lower Central America. It is one of the least herpetological explored countries in Central America and few studies dealing with the herpetofauna of a potion or the entire country have been published. I here update the checklist of the Nicaraguan herpetofauna, present taxonomic revisions of some difficult species complexes, compare the similarities of the composition of the herpetofaunal communities in the major forest formations present in the country within a zoogeographical context, and identify those species with a greater vulnerability risk in Nicaragua. Taxonomy The herpetofauna of Nicaragua currently consists of 244 species representing 134 genera and 42 families with 78 amphibian species representing 35 genera and 15 families, and 166 reptile species representing 99 genera and 27 families, which includes six marine species. Sixteen species (12 amphibians and four reptiles) are endemic to the country. Of the 12 endemic amphibian species, three are here described. In addition, five genera (Anotheca, Cerrophidion, Duellmanohyla, Isthmohyla, and Rhinobothryum) and two species (Rhadinea godmani and Urotheca decipiens) are known to occur both north and south of Nicaragua although there are no voucher specimens of these taxa to confirm their presence in country. I complete a bibliographic research updating the nomenclature changes and provide a brief herpetological history of Nicaragua, a recompilation of all species described upon Nicaraguan material and their current synonymy, the first time each species was recorded from the country, and a list of all recognized subspecies occurring in Nicaragua. I discuss the taxonomic uncertainties among the Nicaraguan populations of amphibians and reptiles and take further detailed taxonomic revisions on selected Nicaraguan species groups from the genera Anolis, Bolitoglossa, and Craugastor along their known distributional range. I describe five new species of herpetofauna (three of which are based on Nicaraguan material), redescribe five species of Anolis (three of which occur in Nicaragua), and provide voucher specimens of five other species for the first time in Nicaragua. In detail: • I studied the pholidosis, morphometrics as well as hemipenis and dewlap morphology in Anolis wermuthi, an anole endemic to the highlands of northern Nicaragua. I examine patterns of geographic variation using discriminant function analysis and discuss the characters that vary both individually and among populations. The results indicate that A. wermuthi is a single species with several disjunct, slightly divergent populations. I provide a standardized description, illustrations of the everted hemipenis of an adult topotype, the male and female dewlap, and a distribution map. I also provide brief descriptions of the localities where this species occurs and some ecological notes. • I studied the pholidosis, morphometrics as well as hemipenis morphology in the Central American anole species Anolis humilis, A. quaggulus, and A. uniformis. The three taxa are distinct in hemipenis morphology. However, very little differentiation in pholidotic and morphometric characters is documented. I document interspecific variation in several characters but with overlap of the documented ranges. A discriminant function analysis based on five pholidotic characters yielded a scatter diagram that showed large overlap between the clusters of the three taxa. I provide head scalation illustrations, an identification key, a distribution map, and standardized descriptions of the commonly distributed in Nicaragua A. quaggulus as well as of the other two species. • I describe two new species of anoles (genus Anolis) from Panama formerly referred to as Anolis limifrons. The two new species, Anolis apletophallus and Anolis cryptolimifrons, differ from A. limifrons by having a large bilobed hemipenis (small and unilobed in A. limifrons). The new species differ from each other in male dewlap size and coloration. I provide illustrations of the head scalation, everted hemipenis, and dewlap, an identification key, a distribution map, and standardized descriptions of the commonly distributed in Nicaragua A. limifrons and the two new species described herein. • I describe two new species of salamanders of Bolitoglossa from southern Nicaragua. Bolitoglossa indio is known from Río Indio in the lowlands of the Río San Juan area and Bolitoglossa insularis from the premontane slopes of Volcán Maderas on Ometepe Island. The two new species are of unknown affinities but both differ from their congeners in coloration. Bolitoglossa indio is most similar to B. mexicana and B. odonnelli from which differ by having both broad dorsolateral pale brown stripes not clearly delimited in outline. Bolitoglossa insularis is most similar to B. mombachoensis and B. striatula from which differ by the absence of dark or light defined stripes on dorsum and venter. • I describe a new species of frog of the genus Craugastor from Río San Juan, Nicaragua. The new species, Craugastor chingopetaca, is assigned to the fitzingeri group and differs from most Central American species of that group by the absence of a midgular pale stripe. Within the fitzingeri group it is most similar to C. crassidigitus and C. talamancae from which it differs in several morphological characteristics such as more extensive webbing, retuse disk covers on some digits, and relative toe length. • I provide voucher specimens of Cochranella spinosa, Kinosternon angustipons, Mesaspis moreletii, Cnemidophorus lemniscatus and Adelphicos quadrivirgatum for the first time in Nicaragua. I include descriptions, illustrations, and brief ecological notes for the five new country records. Zoogeography Based on the concept of ecological formations proposed by HOLDRIDGE (1967), nine forest formations are found in Nicaragua. Of the total number of terrestrial species of herpetofauna found in Nicaragua, 131 species (55.0%) occur in Lowland Wet Forest, 21 of which (8.8%) are restricted to this forest formation, 168 species (70.6%) occur in Lowland Moist Forest, 15 of which (6.3%) are restricted to this forest formation, 84 species (35.3%) occur in Lowland Dry Forest, four of which (1.7%) are restricted to this forest formation, 47 species (19.7%) occur in Lowland Arid Forest, with no species restricted to this forest formation, 59 species (24.8%) occur in Premontane Wet Forest, three of which (1.3%) are restricted to this forest formation, 116 species (48.7%) occur in Premontane Moist Forest, 10 of which (4.2%) are restricted to this forest formation, 51 (21.4%) species occur in Premontane Dry Forest, with no species restricted to this forest formation, 13 species (5.5%) occur in Lower Montane Wet Forest, two of which (0.8%) are restricted to this forest formation, and 50 species (21.0%) occur Lower Montane Moist Forest, seven of which (2.9%) are restricted to this forest formation. The Coefficient of Biogeographic Resemblance algorithm show a distinct composition of the herpetofauna from the isolated highlands of northeastern Nicaragua, which is characterized by a high proportion of endemic species. Two other clusters are evident when analyzing the herpetofaunal similarities among Nicaragua, the Pacific versant and the central mountains and the Atlantic lowlands. In addition, the Pacific lowlands are characterized by a relatively homogeneous composition of the herpetofauna. In contrast, many species have their northern limit of distribution in the Atlantic lowlands with the ranges of most of these species ending in southern Nicaragua. The central mountains constitute the southern limit of distribution of several highland species. In general, there is a greater contribution of reptile than amphibian species to the total herpetofauna present in each forest formation. This unbalance is slightly higher in the dry than in the moist parts of the country. The similarities in the composition of the reptiles between the different forests formations seem to be relatively distinct on an elevation factor, whereas in amphibians similarities might be better explained in correlation with humidity. The total amount of amphibian and reptile species in Nicaragua has a Middle American Element dominance and varies between amphibians and reptiles, with and a greater South American Element influence in anurans and a greater Old Northern Element influence in reptiles. In general, there is a greater percentage of species with a South American Element in extreme southeastern Nicaragua with a decreasing tendency towards northern Nicaragua. Taking in account the geography and geologic history of Nicaragua as well as the known Central American dispersal routes, I identify species of probable occurrence in Nicaragua as well as those places with a greater potential to hold undescribed endemic species. Conservation In Nicaragua, no amphibian or reptile populations are entirely free from anthropogenic impact. I determine the endangerment level of all Nicaraguan amphibian and reptile species using the IUCN categorizations and the Environmental Vulnerability Scores. Seventy-six species (31.9%) of Nicaraguan amphibians and terrestrial reptiles have high vulnerability, 118 (49.6%) medium vulnerability, and 44 (18.5%) low vulnerability. Eighteen species (7.4% of the total herpetofauna) are unknown from protected areas, including 13 high vulnerability species (three are endemic), four medium vulnerability species, and one low vulnerability species. To preserve the future of Nicaragua’s amphibians and reptiles, every species should reside in at least one protected area, the protected areas must be guarded, and monitoring programs are needed to detect changes in amphibian and reptile populations, prioritizing highly vulnerable species.
Poster presentation: Introduction Rhythmic synchronization of neural activity in the gamma-frequency range (30–100 Hz) was observed in many brain regions; see the review in [1]. The functional relevance of these oscillations remains to be clarified, a task that requires modeling of the relevant aspects of information processing. The temporal correlation hypothesis, reviewed in [2], proposes that the temporal correlation of neural units provides a means to group the neural units into so-called neural assemblies that are supposed to represent mental objects. Here, we approach the modeling of the temporal grouping of neural units from the perspective of oscillatory neural network systems based on phase model oscillators. Patterns are assumed to be stored in the network based on Hebbian memory and assemblies are identified with phase-locked subset of these patterns. Going beyond foregoing discussions, we demonstrate the combination of two recently discussed mechanisms, referred to as "acceleration" [3] and "pooling" [4]. The combination realizes in a complementary manner a competition for activity on a local scale, while providing a competition for coherence among different assemblies on a non-local scale. ...
Zusammenfassung Die Alzheimersche Krankheit (AD) ist mit 60% die am häufigsten auftretende Art der Demenz. Weltweit sind ca. 24 Mio. Menschen von der neurodegenerativen Krankheit betroffen, welche sich durch den Verlust der kognitiven Fähigkeiten auszeichnet. Es gibt zwei Ausprägungen der Demenz, zum einen die sporadische Verlaufsform, die bei Menschen in einem Alter ab 65 Jahren auftritt und zum anderen die familiäre Alzheimersche Krankheit (FAD), die schon weitaus jüngere Menschen betrifft und auf genetische Mutationen zurück zu führen ist. Beide Formen der Demenz zeigen den gleichen neuropathologische Phänotyp, der zur Ausbildung von extrazellulären Plaques und intrazellulären Neurofibrillen führt. Durch die Entstehung der Plaques und der Neurofibrillen werden die Verbindungen zwischen den einzelnen Neuronen verringert und die Neuronen sterben ab. Für das Auftreten der FAD sind Mutationen in den Genen des Amyloid Vorläufer Proteins (APP, Substrat) sowie der Aspartatprotease Einheit des γ-Sekretase Komplexes, Presenilin 1 (PS1) oder Presenilin 2 (PS2), verantwortlich. Die γ-Sekretase ist ein membranständiger Komplex bestehend aus den vier Untereinheiten PS1 oder PS2, Nicastrin (Nct), Aph-1 und Pen-2. Um ausreichende Informationen über den γ-Sekretase Komplex bezüglich seiner Interaktionsflächen, seines Katalysemechanismus und seiner Substraterkennung zu erhalten, wäre es hilfreich seine 3 Dimensionale Struktur aufzuklären, wozu große Mengen der sauberen und homogenen Proteine benötigt werden. Die Herstellung von ausreichenden Proteinmengen stellt derzeit aber einen Engpass für die strukturelle und funktionelle Charakterisierung des γ-Sekretase Komplexes in-vitro dar. Alzheimer’s disease (AD) is the most common cause of dementia, which affects 24 million people worldwide. It is a neurodegenerative disorder, which occurs either in its most common form in people over 65 years or in the rare early-onset familial AD (FAD). Responsible for the autosomal dominant FAD are mutations in the genes encoding for the β-amyloid precursor protein (APP) and the two homologues integral membrane proteins Presenilin 1 (PS1) and Presenilin 2 (PS2). The two PSs are major but alternative components of the intramembrane aspartyl protease γ-secretase. Further components are the membrane proteins Nicastrin (Nct), Aph-1 and Pen-2. Production of sufficient amounts of protein samples is still the major bottleneck for the detailed functional and structural in-vitro characterization of the γ-secretase complex. Due to toxicity, stability and targeting problems, the overproduction of MPs in conventional in-vivo systems often has only limited success. Therefore, efficient expression protocols using the cell-free (CF) system were established in this work. After optimization, I was able to produce up to milligram amounts of the single proteins PS1 and PS2, the cleavage products PS1-NTF and PS1-CTF, and Pen-2. The in-vitro produced γ-secretase subunits were further characterized, concerning their purity, secondary fold, thermal stability and homogeneity. Highest purities with over 90% after affinity chromatography could be achieved for PS1-CTF and Pen-2. Reconstitution of PS1, PS1-NTF, PS1-CTF and Pen-2 into E. coli liposomes results in a homogeneously distribution, which gives evidence for a structural folding. This was confirmed by CD spectroscopy of PS1-CTF and Pen-2. The thermal stability of Pen-2 shows a transition at 68°C, whereas PS1-CTF is stable up to 95°C. Both proteins show in addition homogeneous elution profiles investigated by analytical SEC and exhibit a monomeric (Pen-2) or dimeric (PS1-CTF) character analyzed by blue native PAGE. Different methods were performed to get evidence about the assembly of the complex, like pull-down experiments, immunoprecipitation, co-expression of radioactive labeled subunits and titration assays by liquid-state NMR. First hints for an interaction of the CF synthesized proteins could be observed by co-expression. Supplemental, Pen-2 and CTF could be purified in sufficient amounts and to apparent homogeneity that allow structural approaches by X-ray crystallography and liquid-state NMR spectroscopy. First conditions for protein crystals were achieved for Pen-2 and structural investigations of PS1-CTF by liquid-state NMR could be performed after optimization of the expression-, purification- and detergent conditions.
Poster presentation: Introduction We here address the problem of integrating information about multiple objects and their positions on the visual scene. A primate visual system has little difficulty in rapidly achieving integration, given only a few objects. Unfortunately, computer vision still has great difficultly achieving comparable performance. It has been hypothesized that temporal binding or temporal separation could serve as a crucial mechanism to deal with information about objects and their positions in parallel to each other. Elaborating on this idea, we propose a neurally plausible mechanism for reaching local decision-making for "what" and "where" information to the global multi-object recognition. ...
Poster presentation: Introduction We here focus on constructing a hierarchical neural system for position-invariant recognition, which is one of the most fundamental invariant recognition achieved in visual processing [1,2]. The invariant recognition have been hypothesized to be done by matching a sensory image of a particular object stimulated on the retina to the most suitable representation stored in memory of the higher visual cortical area. Here arises a general problem: In such a visual processing, the position of the object image on the retina must be initially uncertain. Furthermore, the retinal activities possessing sensory information are being far from the ones in the higher area with a loss of the sensory object information. Nevertheless, with such recognition ambiguity, the particular object can effortlessly and easily be recognized. Our aim in this work is an attempt to resolve such a general recognition problem. ...
Poster presentation: The brain is autonomously active and this self-sustained neural activity is in general modulated, but not driven, by the sensory input data stream [1,2]. Traditionally one has regarded this eigendynamics as resulting from inter-modular recurrent neural activity [3]. Understanding the basic modules for cognitive computation is, in this view, the primary focus of research and the overall neural dynamics would be determined by the the topology of the intermodular pathways. Here we examine an alternative point of view, asking whether certain aspects of the neural eigendynamics have a central functional role for overall cognitive computation [4,5]. Transiently stable neural activity is regularly observed on the cognitive time-scale of 80–100 ms, with indications that neural competition [6] plays an important role in the selection of the transiently stable neural ensembles [7], also denoted winning coalitions [8]. We report on a theory approach which implements these two principles, transient-state dynamics and neural competition, in terms of an associative neural network with clique encoding [9]. A cognitive system [10] with a non-trivial internal eigendynamics has two seemingly contrasting tasks to fulfill. The internal processes need to be regular and not chaotic on one side, but sensitive to the afferent sensory stimuli on the other side. We show, that these two contrasting demands can be reconciled within our approach based on competitive transient-state dynamics, when allowing the sensory stimuli to modulate the competition for the next winning coalition. By testing the system with the bars problem, we find an emerging cognitive capability. Only based on the two basic architectural principles, neural competition and transient-state dynamics, with no explicit algorithmic encoding, the system performs on its own a non-linear independent component analysis of input data stream. The system has rudimentary biological features. All learning is local Hebbian-style, unsupervised and online. It exhibits an ever-ongoing eigendynamics and at no time is the state or the value of synaptic strengths reset or the system restarted; there is no separation between training and performance. We believe that this kind of approach – cognitive computation with autonomously active neural networks – to be an emerging field, relevant both for system neuroscience and synthetic cognitive systems.
Background Multidirectional interactions in social (or communication) networks can have a profound effect on mate choice behavior. For example, Poecilia mexicana males show weaker expression of mating preferences when being observed by an audience male. It was suggested that this behavior is an adaptation to reduce sperm competition risk, which arises because commonly preferred female phenotypes will receive attention also by surrounding males, and/or because the audience male can copy the focal male's mate choice. Do P. mexicana males indeed respond to perceived sperm competition risk? We gave males a choice between two females and repeated the tests under one of the following conditions: (1) during the 2nd part of the tests an empty transparent cylinder was presented (control); (2) an audience male inside the cylinder observed the focal male throughout the 2nd part, or (3) the audience male was presented only before the tests, but could not eavesdrop during the actual choice tests (non-specific sperm competition risk treatments); (4) the focal male could see a rival male sexually interacting with the previously preferred, or (5) with the non-preferred female before the 2nd part of the tests (specific sperm competition risk treatments). Results When comparing the strength of individual male preferences between the 1st and 2nd part of the tests (before and after presentation of an audience), male preferences declined slightly also during the control treatment (1). However, the decrease in strength of male preferences was more than two-fold stronger in audience treatment (2), i.e., with non-specific sperm competition risk including the possibility for visual eavesdropping by the audience male. No audience effect was found in treatments (3) and (5), but a weak effect was also seen when the focal male had seen the previously preferred female sexually interact with a rival male (treatment 4; specific sperm competition risk). Conclusions When comparing the two 'non-specific sperm competition risk' treatments (2 and 3), a very strong effect was found only when the audience male could actually observe the focal male during mate choice in treatment (2). This suggests that focal males indeed attempt to conceal their mating preferences in the visual presence of other males so as to avoid mate choice copying. When there is no potential for eavesdropping [treatment (3)], non-specific specific sperm competition risk seems to play a minor or no role. Congruent with studies on other poeciliid species, our results also show that P. mexicana males respond to perceived specific sperm competition risk, and tend to share their mating effort more equally among females when the resource value of their previously preferred mate decreases (after mating with a rival male). However, this effect is comparatively weak.
This paper addresses the question whether close borrower-lender relationships, so called hausbank-relationships, facilitate the funding and beneficial development of SME. To this end, we derive a model which relates a firm's growth rate to its need for external funds and subsequently compute the firms that exceed their predicted growth rate. We then use this measure to identify specific characteristics that are associated with long- and short-term financing of firm growth, in particular the influence of relationship lending. We find that close ties with savings banks predict firms' access to external finance to fund growth. Moreover, the long-term liabilities of firms with hausbank-relationships almost double those with multiple relationships while the overall leverage is about the same. In turn, we find an strong empirical relationship between the provision of long-term funds and firm growth. Keywords: small business lending, credit access, public banks JEL Classifications: G21, D21
Despite the well-known importance of ribonucleic acids (RNA) in cell biology, it is astounding to realize the pace at which new fundamental functions of RNAs have been discovered. One of the fundamental reasons for the multitude of functions of RNA is the property of RNA to adopt different conformations or folds. The primary sequence of RNA, a linear polymer built from four different repetition units, can fold into alternate secondary structure motifs which in turn form alternate long-range interactions in complex tertiary structures. Ligands such as metal ions or small molecular weight metabolites and also proteins or peptides can bind to RNA and induce the changes in tertiary conformation. For example, in the cell, RNA participates in gene regulation in the form of riboswitches. Riboswitches are found in untranslated regions of messenger RNA (mRNA) and adopt alternate conformations depending on the presence or absence of specific metabolites. If a metabolite is present above a specific concentration, it induces a conformational change in the respective riboswitch by binding and thereby alters gene expression. Another example is the RNA thermometer which participates in the cell translational mechanism by a similar strategy. Translation initiation requires the binding of RNA thermometers to the ribosome. The ribosome binding region is located in the 5’ untranslated region of mRNA. At low temperatures this region is prevented from binding to the ribosome by forming basepairs. At higher temperatures, these basepairs dissociate allowing ribosome binding and subsequent translation. Therefore, the characterization and delineation of the kinetics and pathway of RNA folding is important to understand the function of RNA and is an important contribution to fundamentally understand RNA’s role in the cell. RNA conformational transitions occur over a wide range of timescales. Depending on the timescale, various biophysical techniques are used to study RNA conformational transitions. In these biophysical studies, achieving good structural and temporal resolution constitute frequently encountered challenges or limitations. For example, single molecule FRET spectroscopy provides high temporal resolution in the milliseconds at high sensitivity but lacks atomic resolution. Recent advances in the field of Nuclear Magnetic Resonance (NMR) spectroscopy have enabled the elucidation of tertiary folding events to be characterized with atomic resolution. This thesis involves the use of NMR spectroscopy to characterize the folding of RNA molecules. Kinetics experiments require rapid initiation of the kinetics followed by monitoring of the reaction. In this thesis, two different folding initiation techniques have been applied and coupled to the subsequent detection of RNA folding using NMR spectroscopy, namely, photocaging and rapid mixing. The method of photocaging is well established (Kuhn and Schwalbe, 2000) and builds on the following principle: A photolabile moiety is attached to a molecule that prevents a specific interaction. Upon irradiation of the molecule with the photolabile group using laser light at a specific wave length, at which the molecule of interest is not absorbing, the protecting group is released. In our group, together with the group of S. Pitsch, ETH Lausanne, we could "cage" RNA at its equilibrium state by a photolabile molecule (similar work has been carried out in the group of A. Heckel). Rapid and traceless release of the photolabile precursor compound by a laser pulse releases the RNA to fold into its native state; the build-up of the native state of the RNA is monitored by NMR signals that are uniquely characteristic for the native state of the RNA. By optically coupling a laser source to an NMR magnet, the above procedure can take place in situ and the kinetics recorded by NMR. Several different molecules can be caged: The photocage can be attached to RNA. Then, a modified photolabile nucleotide can be placed at strategic positions of a target RNA whose folding properties is to be studied. The photocage can also be attached to a ligand: if folding is dependent on ligand binding then the ligand can be modified to carry a photosensitive unit whose degradation allows binding to RNA. In this thesis, an alternative method for photocaging is introduced. Here, metal ions essential for folding of the RNA are photocaged using the photolabile chelating agent Dimethyl-nitrophen (DMN). Photolysis of DMNr releases the metal ion, thereby RNA folding is initiated. In the rapid-mixing technique, one of (several) components required for proper folding of the RNA is rapidly injected into an NMR sample in situ by the use of a pneumatic injection device. ...
This paper gives a brief overview of computation models for data stream processing, and it introduces a new model for multi-pass processing of multiple streams, the so-called mp2s-automata. Two algorithms for solving the set disjointness problem with these automata are presented. The main technical contribution of this paper is the proof of a lower bound on the size of memory and the number of heads that are required for solving the set disjointness problem with mp2s-automata.
The study of the electromagnetic structure of hadrons plays an important role in understanding the nature of matter. In particular the emission of lepton pairs out of the hot and dense collision zone in heavy-ion reactions is a promising probe to investigate in-medium properties of hadrons and in general the properties of matter under such extreme conditions. The first experimental observation of an enhanced di-electron yield in the invariant-mass region 0:3 - 0:7 GeV/c2 in p+Be collisions at 4:9 GeV/u beam energy [2] was announced by the DLS collaboration [1]. Recent results of the HADES collaboration show a moderate enhancement above n Dalitz decay contributions for 12C+12C at 1 and 2 GeV/u [3, 4] confirming the DLS results. There are several theoretical explanations of this observation, most of them focusing on possible in-medium modifications of the properties of vector mesons. At low beam energies the question whether the observed excess is related to any in-medium effects remains open because of uncertainties in the description of elementary di-electron sources. In this work the di-electron production in p+p and d+p reactions at a kinetic beam energy of 1:25 GeV/u measured by the HADES spectrometer is discussed. At Ekin = 1:25 GeV/u, i.e. below the n meson production threshold in proton-proton reactions, the delta Dalitz decay is expected to be the most abundant source above the pi 0 Dalitz decay region. The observed large difference in di-electron production in p+p and d+p collisions suggests that di-electron production in the d+p system is dominated by the n+p interaction. In order to separate delta Dalitz decays and np bremsstrahlung the di-electron yield observed in p+p and n+p reactions, both measured at the same beam energy, has been compared. The main interest here is the investigation of iso-spin effects in baryonic resonance excitations and the off-shell production of vector mesons [5]. We indeed observe a large difference in di-electron production in p+p and n+p reactions. Results of these studies will be compared to recent calculations. We will also present our experimentally defined cocktail for heavy-ion data. At much higher beam energies experimental results of the CERES [6] and NA60 [7] collaborations also show an enhancement in the invariant mass region 0:3 - 0:7 GeV/c2, in principle similar to the situation in DLS. A strong excess of lepton pairs observed by recent high energy heavy-ion dilepton experiments hint to a strong influence of baryons, however no data exist at highly compressed baryonic matter, achievable in heavy-ion collisions from 8 - 45 GeV/u beam energy. These conditions would allow to study the expected restoration of chiral symmetry by measuring in-medium modifications of hadronic properties, an experimental program which is foreseen by the future CBM experiment at FAIR. The experimental challenge is to suppress the large physical background on the one hand and to provide a clean identification of electrons on the other hand. In this work, strategies to reduce the combinatorial background in electron pair measurements with the CBM detector are discussed. The main goal is to study the feasibility of effectively reducing combinatorial background with the currently foreseen experimental setup, which does not provide electron identification in front of the magnetic field.
We analyze a national sample of Americans with respect to their debt literacy, financial experiences, and their judgments about the extent of their indebtedness. Debt literacy is measured by questions testing knowledge of fundamental concepts related to debt and by selfassessed financial knowledge. Financial experiences are the participants’ reported experiences with traditional borrowing, alternative borrowing, and investing activities. Overindebtedness is a self-reported measure. Overall, we find that debt literacy is low: only about one-third of the population seems to comprehend interest compounding or the workings of credit cards. Even after controlling for demographics, we find a strong relationship between debt literacy and both financial experiences and debt loads. Specifically, individuals with lower levels of debt literacy tend to transact in high-cost manners, incurring higher fees and using high-cost borrowing. In applying our results to credit cards, we estimate that as much as one-third of the charges and fees paid by less knowledgeable individuals can be attributed to ignorance. The less knowledgeable also report that their debt loads are excessive or that they are unable to judge their debt position. JEL Classification: D14, D91
Local interactions between particles of a collection causes all particles to reorganize in new positions. The purpose of this paper is to construct an energy-based model of self-organizing subgroups, which describes the behavior of singular local moves of a particle. The present paper extends the Hegselmann-Krause model on consensus dynamics, where agents simultaneously move to the barycenter of all agents in an epsilon neighborhood. The Energy-based model presented here is analyzed and simulated on finite metric space. AMS Subject Classifications:81T80; 93A30; 37M05; 68U20
Background: The immune system is a complex adaptive system of cells and molecules that are interwoven in a highly organized communication network. Primary immune deficiencies are disorders in which essential parts of the immune system are absent or do not function according to plan. X-linked agammaglobulinemia is a B-lymphocyte maturation disorder in which the production of immunoglobulin is prohibited by a genetic defect. Patients have to be put on life-long immunoglobulin substitution therapy in order to prevent recurrent and persistent opportunistic infections. Methodology: We formulate an immune response model in terms of stochastic differential equations and perform a systematic analysis of empirical therapy protocols that differ in the treatment frequency. The model accounts for the immunoglobulin reduction by natural degradation and by antigenic consumption, as well as for the periodic immunoglobulin replenishment that gives rise to an inhomogeneous distribution of immunoglobulin specificities in the shape space. Results are obtained from computer simulations and from analytical calculations within the framework of the Fokker-Planck formalism, which enables us to derive closed expressions for undetermined model parameters such as the infection clearance rate. Conclusions: We find that the critical value of the clearance rate, below which a chronic infection develops, is strongly dependent on the strength of fluctuations in the administered immunoglobulin dose per treatment and is an increasing function of the treatment frequency. The comparative analysis of therapy protocols with regard to the treatment frequency yields quantitative predictions of therapeutic relevance, where the choice of the optimal treatment frequency reveals a conflict of competing interests: In order to diminish immunomodulatory effects and to make good economic sense, therapeutic immunoglobulin levels should be kept close to physiological levels, implying high treatment frequencies. However, clearing infections without additional medication is more reliably achieved by substitution therapies with low treatment frequencies. Our immune response model predicts that the compromise solution of immunoglobulin substitution therapy has a treatment frequency in the range from one infusion per week to one infusion per two weeks.
This article discusses the divergent status of the two particles lé and lá in the grammar of Konkomba, a Gur language (Niger-Congo) of the Gurma subgroup. While previous studies claim that both particles are focus markers, this author argues that only the particle lá should be analyzed as a pure pragmatic device. Distributional studies suggest that the use of particle lé, on the other hand, is only required under specific focus conditions, and primarily represents a syntactic device.
Identification of caddisfly specimens from Vietnam collected by scientific field staff of the Royal Ontario Museum and the American Museum of Natural History revealed 19 new country records. All but one species were reported from other Oriental region countries, particularly Thailand and Indonesia. However, Goera kawamotonis Kobayashi 1987 was only known from the East Palaearctic region (Japan and Russian Far East). The total number of species now recorded from Vietnam is 400.
When at the end of Hans Sachs' tragedy of Tristrant, dated February 7th, 1553, the herold takes the floor, he calls to the audience to recognize that this is a tragedy, Auß der wird offentlich erkendt, Wie solche unorndliche lieb Hat so ein starck mechtigen trieb, Wo sie einnimbt ein junges hertz Mit bitter angst, senenden schmertz, Darinn sie also heftig wüt, Verkert hertz, sin, vernunft und gmüt, Wird leichtfertig, verwegen gantz, Schlecht seel, lieb, ehr, gut in die schantz, Acht fürbas weder sitten noch tugent, (184,32-185,3) (1) ....
We model the motives for residents of a country to hold foreign assets, including the precautionary motive that has been omitted from much previous literature as intractable. Our model captures many of the principal insights from the existing specialized literature on the precautionary motive, deriving a convenient formula for the economy’s target value of assets. The target is the level of assets that balances impatience, prudence, risk, intertemporal substitution, and the rate of return. We use the model to shed light on two topical questions: The “upstream” flows of capital from developing countries to advanced countries, and the long-run impact of resorbing global financial imbalances
This paper analyzes the risk properties of typical asset-backed securities (ABS), like CDOs or MBS, relying on a model with both macroeconomic and idiosyncratic components. The examined properties include expected loss, loss given default, and macro factor dependencies. Using a two-dimensional loss decomposition as a new metric, the risk properties of individual ABS tranches can directly be compared to those of corporate bonds, within and across rating classes. By applying Monte Carlo Simulation, we find that the risk properties of ABS differ significantly and systematically from those of straight bonds with the same rating. In particular, loss given default, the sensitivities to macroeconomic risk, and model risk differ greatly between instruments. Our findings have implications for understanding the credit crisis and for policy making. On an economic level, our analysis suggests a new explanation for the observed rating inflation in structured finance markets during the pre-crisis period 2004-2007. On a policy level, our findings call for a termination of the 'one-size-fits-all' approach to the rating methodology for fixed income instruments, requiring an own rating methodology for structured finance instruments. JEL Classification: G21, G28
Algorithmic trading engines versus human traders – do they behave different in securities markets?
(2009)
After exchanges and alternative trading venues have introduced electronic execution mechanisms worldwide, the focus of the securities trading industry shifted to the use of fully electronic trading engines by banks, brokers and their institutional customers. These Algorithmic Trading engines enable order submissions without human intervention based on quantitative models applying historical and real-time market data. Although there is a widespread discussion on the pros and cons of Algorithmic Trading and on its impact on market volatility and market quality, little is known on how algorithms actually place their orders in the market and whether and in which respect this differs form other order submissions. Based on a dataset that – for the first time – includes a specific flag to enable the identification of orders submitted by Algorithmic Trading engines, the paper investigates the extent of Algorithmic Trading activity and specifically their order placement strategies in comparison to human traders in the Xetra trading system. It is shown that Algorithmic Trading has become a relevant part of overall market activity and that Algorithmic Trading engines fundamentally differ from human traders in their order submission, modification and deletion behavior as they exploit real-time market data and latest market movements.
We present a tractable model of the effects of nonfinancial risk on intertemporal choice. Our purpose is to provide a simple framework that can be adopted in fields like representative-agent macroeconomics, corporate finance, or political economy, where most modelers have chosen not to incorporate serious nonfinancial risk because available methods were too complex to yield transparent insights. Our model produces an intuitive analytical formula for target assets, and we show how to analyze transition dynamics using a familiar Ramsey-style phase diagram. Despite its starkness, our model captures most of the key implications of nonfinancial risk for intertemporal choice.
The recent financial crisis has led to a vigorous debate about the pros and cons of fair-value accounting (FVA). This debate presents a major challenge for FVA going forward and standard setters’ push to extend FVA into other areas. In this article, we highlight four important issues as an attempt to make sense of the debate. First, much of the controversy results from confusion about what is new and different about FVA. Second, while there are legitimate concerns about marking to market (or pure FVA) in times of financial crisis, it is less clear that these problems apply to FVA as stipulated by the accounting standards, be it IFRS or U.S. GAAP. Third, historical cost accounting (HCA) is unlikely to be the remedy. There are a number of concerns about HCA as well and these problems could be larger than those with FVA. Fourth, although it is difficult to fault the FVA standards per se, implementation issues are a potential concern, especially with respect to litigation. Finally, we identify several avenues for future research. JEL Classification: G14, G15, G30, K22, M41, M42
American households have received a triple dose of bad news since the beginning of the current recession: The greatest collapse in asset values since the Great Depression, a sharp tightening in credit availability, and a large increase in unemployment risk. We present measures of the size of these shocks and discuss what a benchmark theory says about their immediate and ultimate consequences. We then provide a forecast based on a simple empirical model that captures the effects of wealth shocks and unemployment fears. Our short-term forecast calls for somewhat weaker spending, and somewhat higher saving rates, than the Consensus survey of macroeconomic forecasters. Over the longer term, our best guess is that the personal saving rate will eventually approach the levels that preceded period of financial liberalization that began in the late 1970s. Classification: C61, D11, E24
We investigate US households’ direct investment in stocks, bonds and liquid accounts and their foreign counterparts, in order to identify the different participation hurdles affecting asset investment domestically and overseas. To this end, we estimate a trivariate probit model with three further selection equations that allows correlations among unobservables of all possible asset choices. Our results point to the existence of a second hurdle that stock owners need to overcome in order to invest in foreign stocks. Among stockholders, we show that economic resources, willingness to assume greater financial risks, shopping around for the best investment opportunities all increase the probability to invest in foreign stocks. Furthermore, we find that households who seek financial advice from relatives, friends and work contacts are less likely to invest in foreign stocks. This result corroborates the conjecture by Hong et al. (2004) that social interactions should discourage investment in foreign stocks, given their limited popularity. On the other hand, we find little evidence for additional pecuniary or informational costs associated with investment in foreign bonds and liquid accounts. Finally, we show that ignoring correlations of unobservables across different asset choices can lead to very misleading results.
We investigate the effects of both trust and sociability for stock market participation, the role of which has been examined separately by existing finance literature. We use internationally comparable household data from the Survey of Health, Ageing and Retirement in Europe supplemented with regional information on generalized trust from the World Value Survey and on specific trust to financial institutions from Eurobarometer. We show that trust and sociability have distinct and sizeable positive effects on stock market participation and that sociability is likely to partly balance the discouragement effect on stockholding induced by low generalized trust in the region of residence. We also show that specific trust in advice given by financial institutions represents a prominent factor for stock investing, compared to other tangible features of the banking environment. Probing further into various groups of households, we find that sociability can induce stockholding among the less well off in Sweden, Denmark, and Switzerland where stock market participation is widespread. On the other hand, the effect of generalized trust is strong in countries with limited participation and low average trust like Austria, Spain, and Italy, offering an explanation for the remarkably low participation rates of the wealthy living therein.
In the New-Keynesian model, optimal interest rate policy under uncertainty is formulated without reference to monetary aggregates as long as certain standard assumptions on the distributions of unobservables are satisfied. The model has been criticized for failing to explain common trends in money growth and inflation, and that therefore money should be used as a cross-check in policy formulation (see Lucas (2007)). We show that the New-Keynesian model can explain such trends if one allows for the possibility of persistent central bank misperceptions. Such misperceptions motivate the search for policies that include additional robustness checks. In earlier work, we proposed an interest rate rule that is near-optimal in normal times but includes a cross-check with monetary information. In case of unusual monetary trends, interest rates are adjusted. In this paper, we show in detail how to derive the appropriate magnitude of the interest rate adjustment following a significant cross-check with monetary information, when the New-Keynesian model is the central bank’s preferred model. The cross-check is shown to be effective in offsetting persistent deviations of inflation due to central bank misperceptions. Keywords: Monetary Policy, New-Keynesian Model, Money, Quantity Theory, European Central Bank, Policy Under Uncertainty
We reconsider the issue of price discovery in spot and futures markets. We use a threshold error correction model to allow for arbitrage operations to have an impact on the return dynamics. We estimate the model using quote midpoints, and we modify the model to account for time-varying transaction costs. We find that the futures market leads in the process of price discovery. The lead of the futures market is more pronounced in the presence of arbitrage signals. Thus, when the deviation between the spot and the futures market is large, the spot market tends to adjust to the futures market.
The budget constraint requires that, eventually, consumption must adjust fully to any permanent shock to income. Intuition suggests that, knowing this, optimizing agents will fully adjust their spending immediately upon experiencing a permanent shock. However, this paper shows that if consumers are impatient and are subject to transitory as well as permanent shocks, the optimal marginal propensity to consume out of permanent shocks (the MPCP) is strictly less than 1, because buffer stock savers have a target wealth-to-permanent-income ratio; a positive shock to permanent income moves the ratio below its target, temporarily boosting saving. Keywords: Risk, Uncertainty, Consumption, Precautionary Saving, Buffer Stock Saving, Permanent Income Hypothesis.
We use a novel disaggregate sectoral euro area dataset with a regional breakdown that allows explicit estimation of the sectoral component of price changes (rather than interpreting the idiosyncratic component as sectoral as done in other papers). Employing a new method to extract factors from over-lapping data blocks, we find for our euro area data set that the sectoral component explains much less of the variation in sectoral regional inflation rates and exhibits much less volatility than previous findings for the US indicate. Country- and region-specific factors play an important role in addition to the sector-specific factors. We conclude that sectoral price changes have a “geographical” dimension, as yet unexplored in the literature, that might lead to new insights regarding the properties of sectoral price changes.
This paper reviews the rationale for quantitative easing when central bank policy rates reach near zero levels in light of recent announcements regarding direct asset purchases by the Bank of England, the Bank of Japan, the U.S. Federal Reserve and the European Central Bank. Empirical evidence from the previous period of quantitative easing in Japan between 2001 and 2006 is presented. During this earlier period the Bank of Japan was able to expand the monetary base very quickly and significantly. Quantitative easing translated into a greater and more lasting expansion of M1 relative to nominal GDP. Deflation subsided by 2005. As soon as inflation appeared to stabilize near a rate of zero, the Bank of Japan rapidly reduced the monetary base as a share of nominal income as it had announced in 2001. The Bank was able to exit from extensive quantitative easing within less than a year. Some implications for the current situation in Europe and the United States are discussed.
The documentation of life on Earth, that is, the inventorization of nature and the naming and classification of organisms found therein, is a major task for biologists today and a fundamental precondition for nature conservation efforts. This study aimed at contributing to the inventory of amphibians and reptiles in selected, previously understudied ecoregions of Bolivia. I strove to document diversity patterns and seek possible ecological and historical reasons for these patterns. Special attention was paid to the Chiquitano Region situated in the eastern lowlands of Bolivia in a climatic transition zone between the humid evergreen Amazon Forests and the deciduous thorn-scrub vegetation of the Gran Chaco. In congruence with its location in the transition zone, the Chiquitano Region displays a mosaic of habitats: The vegetation is dominated by the endemic Chiquitano Dry Forest, which is probably the largest extant patch of Seasonal Dry Tropical Forest, with enclaves of savanna, the western outliers of the Cerrado biome of central Brazil. Taxonomic revisions: The taxonomic data in this study are used as a tool to measure biodiversity, to assess biogeographic relationships, and to evaluate conservation needs. Since all is predicated on the taxonomic decisions made, an adequate taxonomy is essential, and taxonomy can be regarded as the foundation of this study. The methodology encompassed a variety of herpetological field techniques, such as different survey methods, preparation and documentation of voucher specimens, recording of frog calls, and herpetological laboratory techniques, such as morphology, molecular procedures with mtDNA, phylogenetic analyses, and bioacoustic analysis and descriptions of frog calls. A total of 1251 specimens belonging to 200 species were obtained during this study, including 87 amphibian and 123 reptile species. This constitutes about 36% of the herpetofauna currently known for Bolivia, about 34% of the amphibians currently known for Bolivia and about 40% of the reptiles, respectively. In the course of this study, a new species of frog was described from the study site Caparu in the eastern lowlands of Bolivia; this species, Hydrolaetare caparu Jansen, Gonzales & G. Köhler 2007, differs from the other two congeners in external morphology (e.g., lateral fringes and relative length of fingers, size of palmar tubercle, webbing of toes, and colouration) and advertisement call. Two new colubrid snake species were also described from the study site San Sebastián. Thus far, both are known only from the Chiquitano Region, Provincia Ñuflo de Chávez. Phalotris sansebastiani Jansen & G. Köhler 2008 differs from all the other species in the genus in having a triangular projection of the red snout colouration reaching onto the parietals. Xenopholis werdingorum Jansen, Gonzales & G. Köhler 2009 can be identified as a member of the genus Xenopholis by its vertebral morphology. It differs from the other two species of Xenopholis in having a unique uniform dorsal colour pattern, and from X. scalaris in having two prefrontals and a narrow septum within the neural spine and perpendicular to its long axis as evident in the x-ray images. A review of a small collection of pitvipers from different lowland localities and from the Inter-Andean dry valleys of the region of Pampagrande revealed one new species of Bothrops and one of Bothrocophias (both to be formally described elsewhere). The two pitviper species differ morphologically and genetically from their congeners. The results of a brief review of a small collection of frogs of the genus Scinax (Anura: Hylidae) from different localities in the lowlands, together with analyses of their bioacoustics, suggest an unknown cryptic diversity in Bolivian species of Scinax cf. fuscomarginatus and allies. However, further studies are necessary to clarify the taxonomic status of these populations. In addition, this study provides new data on the morphology (e.g., pholidosis) of snakes, many of them previously known only from few museum specimens. Keys to the Bolivian lizard species of Cercosaura and the Bolivian snake species of Chironius, Clelia, Liophis, Lystrophis, Phalotris, and Xenodon are presented here for the first time. New information on distribution includes many range extensions of amphibian and reptile species, such as five new country records (one frog species, four snake species) and six new departmental records (two frog species, four snake species). Observations on ecology and natural history: Several observations on ecology and natural history were made during field work. Visual signaling, an aspect of territorial behavior that was already known for several species of the genus Phyllomedusa, could be described for the first time for Phyllomedusa boliviana (Jansen & J. Köhler 2007). Furthermore, during audio surveys of an anuran community at the study site San Sebastián from 2005 to 2007, a decline of certain amphibian populations was observed in the rainy season 2006/2007 (Jansen et al., in press). This is possibly related to an extreme drought in the dry season of 2006 where 158 consecutive days without rainfall were recorded. In addition, a new method for measuring intensity of anuran choruses by means of a continuous sound pressure metre was developed (Jansen 2009). The method was suitable to detect calling phenology (during one night), as well as differences in calling activity (between two nights). Biodiversity and biogeographical relationships: Species lists were compiled at the six study sites Pampagrande, Los Volcanes, San Sebastián, Caparú, El Espinal und El Corbalan. The total amphibian and reptile species numbers observed ranged from 37 to 101 with the highest species numbers in San Sebastián (101) and Caparú (89) and the lowest in Los Volcanes (37) and El Espinal (41). A preliminary species list of the herpetofauna of the Chiquitano Region was presented, including 60 amphibian and 84 reptile species. The majority of the amphibians of the Chiquitano Region are classified predominantly as inhabitants of open formations (41 species, 68.3%). Interestingly, even the majority of species recorded from the Chiquitano Dry Forest (32 species) are usually associated with open formations (22 species, 66.7%), followed by the number of species associated with open and forest formations (8 species, 24.4%). Only two of the observed species (6.0%) are predominant forest dwellers. The amphibian assemblage of the Chiquitano Region is most similar in composition to that of the Cerrado biome: 46 species (76.7%) occur in the Cerrado as well, and three species are regarded as Cerrado endemics (5.0%). The Chiquitano Region shares considerably fewer amphibian species with the other biomes (Amazon: 22 species, 36.7%; Gran Chaco: 13 species, 21.7%; Caatinga: 16 species, 26.7%). The reptile assemblage also has significant affinities to the Cerrado, which can be seen in the high proportion of reptile species distributed in that biome (68 species; 81.0%). Affinities to the other biomes are as follows: Amazon (48 species, 57.1%), Chaco (37 species, 40.1%), and Caatinga (30 species, 35.7%). When arranged in mutually exclusive biome categories, reptiles and amphibians showed similar patterns so that the majority of both amphibians and reptiles of the Chiquitano Region can be regarded as widespread. The high proportion of reptile species probably endemic to this region (5 species, 6.0%) is remarkable (i.e. Tropidurus xanthochilus, Apostolepis phillipsi, Phalotris sansebastiani, Xenopholis werdingorum, and Micrurus diana). In an analysis of the biodiversity patterns and biogeographical relationships of the herpetofauna of the study sites, these sites were compared with literature data from 37 localities and included in a presence/absence matrix with a total of 657 amphibian and reptile species in the surrounding South American biomes Amazon, Cerrado and Gran Chaco. The biogeographic relationships between these sites were evaluated using the Coefficient of Biogeographic Resemblance (CBR), cluster analysis, and multidimensional scaling (MDS) of sites. The analyses were first conducted on amphibians and reptiles combined, and than group-specific each for amphibians, reptiles, lizards, and snakes, separately. A “bias-reduced analysis” was developed for a better understanding of the affinities of the amphibians. In this analysis, e.g., the distinct habitat types of the Chiquitano Region, the Chiquitano Dry Forest and the Cerrado were taken into account. Analyses of the biodiversity patterns revealed that the sites in the Amazon comprise highest species numbers, as expected, followed successively by the sites in the Cerrado biome and sites in-between the two biomes. Within the eastern lowlands of Bolivia, the Chiquitano Region is the most rich in species. Comparing it with the other South American sites, the Chiquitano Region has a surprisingly high alpha diversity, especially in amphibians. The microgeographic variation in species composition (beta diversity) in the Chiquitano Region is also remarkably high and obviously related to the mosaic character of the vegetation and habitats. However, the bias-reduced analysis revealed that the amphibian fauna of the open areas and savannas at Hacienda San Sebastián (with 36 species in the Cerrado and pastureland) was one of the most species-rich savanna sites known for amphibians in South America. Considering that the Hacienda San Sebastián site is only ca. 3300 ha (= 1.29 amphibian species per km2), this outcome is particularly suprising. The results of the analyses of the biogeographical relationships suggest that the herpetofauna of Bolivia’s lowlands, including the Beni, the Pantanal and the Chiquitano Region, is as distinct from the herpetofauna of the Gran Chaco, Amazon, and Cerrado as these biomes are from each other. The Chiquitano herpetofauna in particular represents a unique and well-defined herpetofaunal assemblage when compared to all surrounding localities and biomes. This is supported by high CBR-values, findings from the cluster analysis, as well as a clear separation of the Chiquitano sites in the MDS. Biogeographic relations exist in all the surrounding biomes, but are strongest to Cerrado, followed by the Amazon. This study strongly suggests that the Chiquitano herpetofauna is composite and has multiple affinities. This is congruent with a well-defined Chiquitano flora, avifauna and mammalian fauna, suggesting a similar history. The bias-reduced analysis revealed a more detailed picture of the biogeographic relations of the Chiquitano Region, especially the Chiquitano Dry Forest. I argue here that the Chiquitano Dry Forest herpetofauna is a “young”, and “former savanna herpetofauna”. Whereas the Chiquitano Dry Forest is rather poor in amphibian and reptile species, and endemics are lacking from this forest type, the isolated Cerrado enclaves are especially diverse in species and probably contain locally endemic species, such as Phalotris sansebastiani and Xenopholis werdingorum. The colonization of the young Chiquitano Dry Forest may have taken place from savannas by mainly open area species, and only briefly through the Amazon. The results emphasise the importance of bias-reduction in studies of biogeography, e.g., by using group-specific analyses or by taking into account criterias as area size and heterogeneity of compared sites. The different biogeographic patterns of reptiles and amphibians of the Andean valleys indicate a different history of these two groups. In regard to reptiles, dispersals and withdrawals into the valleys in warm humid and dry cool periods in the Pleistocene seem likely, supported by a relation between the valleys and the dry lowland (e.g., Chaco). However, it is more plausible that, during these climatic fluctuations, amphibians migrated to adjacent, more humid regions, such as Yungas. The study verified the known patterns of sister-species pairs in the Inter-Andean Dry Forest and the lowlands. Additionally, pairs of populations with slight differences in morphology were found in the valleys and in the lowlands (Cercosaura parkeri and Xenodon rhapdocephalus). Further studies must test the taxonomic status of these populations. The discovery of new species of Bothrops and Bothrocophias from the Andean valleys has several implications, and possible reasons for the high endemism in the dry valleys are discussed. Conservation and outlook: The high local alpha and beta diversity of the Chiquitano herpetofauna shows that this is a region of complex faunal interaction, which reflects the present heterogeneity of the region, but which is possibly also related to a complex geological and environmental history. The Chiquitano Region can be assessed as a region of distinct regional herpetofaunal diversity charaterised by small scale diversity patterns. It therefore merits recognition as a unique ecoregion, and conservation effort should be increased. Further research is necessary to solve the taxonomic problems addressed in this study. Moreover, future work should be directed towards the development and institution of longterm monitoring programs to evaluate the effects of climate change and changes in land-use on biodiversity, especially that of the Chiquitano Region.
The physiology of our most complex organ, the brain, is still not comprehensively understood. The brain basically serves the processing, storing and binding of external and internal information, and thereby generates amazing phenomena like the understanding of oneself as an individual entitiy. How exactly information is encoded and represented, how individual neurons or networks of neurons actually interact, is a gigantic puzzle, whose pieces were collected since many decades. Subject of scientific discussions are the basic spatiotemporal structures of neuronal representations. Suggestions and observations reach hereby from simple rate coding of individual neurons to synchronous activity of larger ensembles. To approach answers to these questions, our working group has used a combination of different recording techniques that allowed for the comparison of neuronal interactions on different spatial scales. We focused on prefrontal neuronal interactions during visual short-term memory. Herefore two rhesus monkeys had been trained to perform a visual short-term memory task. We measured and recorded their neuronal activity by means of a microelectrode matrix that could be inserted into the cortex via a closable chamber, which had been previously implanted above prefrontal cortex. The acquired signal was separated into two components: a high-frequency component, that represents the spiking output activity of few neurons in the vicinity of each electrode tip (multi-unit activity), and a low-frequency component, that results from dendritic input activity of larger neuronal assemblies (local field potential). From one of the experimental animals we also recorded mass signals of even larger neuronal populations by means of small silverball electrodes, that had been implated into the skull above prefrontal cortex (skull EEG) in the context of a pilot project. In the first subproject, we analyzed the selectivity of output signals with respect to the memorized stimulus and task performance. We compared selectivities of local recording sites (multi-unit activity) with the selectivities of patterns created by the combined activity of all recording sites, thus representing the activity of large and distributed ensembles. Local neuronal activity correlated with the course of the visual short-term memory task, but was not highly discriminative with respect to different visual stimuli. We could show that the population activity was significantly more specific. Concerning task performance, we obtained the same result, albeit less pronounced. Further analyses revealed that the patterns of distributed ensemble activity were only partly based on realtime coordination of neuronal activity, and in addition, did not remain stable across the time course of the short-term memory task. In the second subproject, we focused on the oscillatory behavior of the local field potential. After a time-frequency analysis, we studied different frequency bands concerning stimulus selectivity and task performance of the monkey. We hereby found significant modulations of oscillations in the beta- and gamma-frequency range, that correlated with different periods of the task. Especially for oscillations in beta- and low-gamma-range, we observed phase-locking of oscillations between different recording sites, which could play an important role as internal clock to coordinate spatially separate activity. Local high-gamma oscillations themselves seemed to be important for the maintenance of information. These results could be partly confirmed by mass signals of EEG. In sum, our results support the hypothesis that information is represented in the brain by means of concerted activity of spatially distributed neuronal ensembles. This activity again appears to be coordinated by oscillatory activity in beta- and low-gamma-frequency ranges. A deeper understanding of central nervous information processing could contribute to better treatment of diseases like Parkinson’s, Alzheimer’s as well as epilepsy, and neuropsychiatric disorders like schizophrenia.
Is the digital future a blessing for philologists, especially those working the vast area of Germanic Languages & Literatures? Or does it rather come with problems that jeopardize philology, in the Germanic and the broader scope? This paper sets out to explore the status quo (1.) of digital source material in Germanic philology, ranging from medieval manuscripts to 21st century e-books and their, at times, highly restricted availability to the scientific community. Do we really face a quantum leap in terms of open access, or is this leap rather confined to those only who pay the exorbitant fees specialist libraries charge for the use of their rare manuscript and book collections? How about Google Books (2.)? Are we in danger of neglecting everything that is (still) missing there? And what is in it for the German scholar? Can we believe that in some years’ time we will be able to get our hands on every source text we desire within seconds since it is only a click away? This paper critically assesses the process and progress of the digitization of mankind’s written records (3.), focusing on problems to be overcome by e.g. medievalists wishing to consult certain source material. This is illustrated by means of the example of how it is not yet possible consult certain materials related to the Franciscan preacher Berthold von Regensburg († 1272). A short concluding summary (4.) highlights perspectives for further thinking and discussion.
At the beginning of every story of murder there is always a body. If the murderer is a serial killer, there is, of course, more than one. More importantly, the bodies left by the serial killer are not likely to be intact and whole. What he leaves behind and what we, the audience, will get to see is the body in pieces, dismembered, scattered. A series of snapshots, partial views, and close-ups, inflicting cold sharp shocks, is all we may glimpse: the head of Benjamin Raspail floating in a jar of formaldehyde in The Silence of the Lambs, a finger removed by the serial killer from his landlord’s hand in Kalifornia, a ziploc bag of fingers recovered from a flooded drainpipe in When The Bough Breaks, a surgically severed hand used to leave misleading fingerprints on a wall at a crime scene in Seven.
Crystals of the title compound, C12H8N2·C7H8O2, were obtained during cocrystallization experiments of a compound with two hydrogen-bond donors (2-hydroxybenzyl alcohol) with another compound containing two hydrogen-bond acceptors (phenanthroline). Unexpectedly, the two molecules do not form dimers with two O—H ... N hydrogen bonds connecting the two molecules. However, one of the hydroxy groups forms a bifurcated hydrogen bond to both phenanthroline N atoms, whereas the other hydroxy group forms an O—H ... O hydrogen bond to a symmetry-equivalent 2-hydroxybenzyl alcohol molecule. In addition, the crystal packing is stabilized by Pi – Pi interactions between the two phenanthroline ring systems, with a centroid–centroid distance of 3.570 Å.
The title compound, C6H5NO2·C6H6O2, crystallizes with one pyridinium-2-carboxylate zwitterion and one molecule of benzene-1,2-diol in the asymmetric unit. The crystal structure is characterized by alternating molecules forming zigzag chains running along the a axis: the molecules are connected by O—H ... O and N—H ... (O,O) hydrogen bonds.
It has become popular for journalists who are trying to sell newspapers, and politicians who are trying to solicit votes, to refer to this financial crisis as the worst since the Great Depression or WWII. I don’t know whether it is the worst or not so will leave that question to the historians and economists of the future once the storm has past. But it is indeed a “storm” as described by Vince Cable, Member of Parliament in his UK bestselling book entitled “The Storm – The World Economic Crisis and What it Means”. He describes this “storm” as a very destructive one displacing jobs, businesses, banks and whole economies from Iceland to the United Kingdom to the United States. I propose to offer a short chronology and summary of the causes of the current economic crisis. Then I will review several of the regulatory responses to the crisis focusing on the Turner Report, the de Larosière Group and certain US Treasury statements. I will offer my critiques of these proposals and then make some predictions of what the financial services industry may look like in the future.
The recent financial crisis has led to a major debate about fair-value accounting. Many critics have argued that fair-value accounting, often also called mark-to-market accounting, has significantly contributed to the financial crisis or, at least, exacerbated its severity. In this paper, we assess these arguments and examine the role of fair-value accounting in the financial crisis using descriptive data and empirical evidence. Based on our analysis, it is unlikely that fair-value accounting added to the severity of the current financial crisis in a major way. While there may have been downward spirals or asset-fire sales in certain markets, we find little evidence that these effects are the result of fair-value accounting. We also find little support for claims that fair-value accounting leads to excessive write-downs of banks’ assets. If anything, empirical evidence to date points in the opposite direction, that is, towards overvaluation of bank assets.
The global financial crisis has lead to a renewed interest in discretionary fiscal stimulus. Advocates of discretionary measures emphasize that government spending can stimulate additional private spending — the so-called Keynesian multiplier effect. Thus, we investigate whether the discretionary spending announced by Euro area governments for 2009 and 2010 is likely to boost euro area GDP by more than one for one. Because of modeling uncertainty, it is essential that such policy evaluations be robust to alternative modeling assumptions and different parameterizations. Therefore, we use five different empirical macroeconomic models with Keynesian features such as price and wage rigidities to evaluate the impact of fiscal stimulus. Four of them suggest that the planned increase in government spending will reduce private spending for consumption and investment purposes significantly. If announced government expenditures are implemented with delay the initial effect on euro area GDP, when stimulus is most needed, may even be negative. Traditional Keynesian multiplier effects only arise in a model that ignores the forward-looking behavioral response of consumers and firms. Using a multi-country model, we find that spillovers between euro area countries are negligible or even negative, because direct demand effects are offset by the indirect effect of euro appreciation.
Recent evaluations of the fiscal stimulus packages recently enacted in the United States and Europe such as Cogan, Cwik, Taylor and Wieland (2009) and Cwik and Wieland (2009) suggest that the GDP effects will be modest due to crowding-out of private consumption and investment. Corsetti, Meier and Mueller (2009a,b) argue that spending shocks are typically followed by consolidations with substantive spending cuts, which enhance the short-run stimulus effect. This note investigates the implications of this argument for the estimated impact of recent stimulus packages and the case for discretionary fiscal policy.
This paper investigates the impact of IT standardization on bank performance based on a panel of 457 German savings banks over the period from 1996 to 2006. We measure IT standardization as the fraction of IT expenses for centralized services over banks' total IT expenses. Bank efficiency, in turn, is measured by traditional accounting performance indicators as well as by cost and profit efficiencies that are estimated by a stochastic frontier approach. Our results suggest that IT standardization is conducive to cost efficiency. The relation is positive and robust for small and medium-sized banks but vanishes for very large banks. Furthermore, our study confirms the often cited computer paradox by showing that total IT expenditures negatively impact cost efficiency and have no influence on bank profits. To the best of our knowledge, this paper is first to empirically explore whether IT standardization enhances efficiency by employing genuine data of banks' IT expenditures. JEL Classification: C23, G21 Keywords: IT standardization, cost and profit efficiency, savings banks
Over the last four decades the literature on bond rating changes and its effects on security prices increased significantly with almost all studies not controlling for the respective reason for those. We therefore investigate the impact of rating events on the stock and the credit default swap (CDS) market incorporating rating reviews and rating changes together with the reason mentioned by the rating agency. Our results for the general effects are in line with prior findings but conditioning on the respective reason shows that the markets’ anticipation of rating actions is largely driven by events due to changes in firms’ operating performance. Furthermore, we provide empirical evidence for the hypothesis in prior literature that a surprise downgrade does not necessarily have to be bad news for stockholders when wealth is transferred from bondholders, but negative rating actions are always bad news for bondholders. The results additionally reveal increasing rating announcement effects by declining credit quality of firms for both rating reviews and changes. JEL Classification: D82, G14, G20. Keywords: Credit Default Swaps, Credit Ratings, Credit Rating Reasons, Event Study.
The objective of this paper is to test the hypothesis that in particular financially constrained firms lease a higher share of their assets to mitigate problems of asymmetric information. The assumptions are tested under a GMM framework which simultaneously controls for endogeneity problems and firms’ fixed effects. We find that the share of total annual lease expenses attributable to either finance or operating leases is considerably higher for financially strained as well as for small and fast-growing firms – those likely to face higher agency-cost premiums on marginal financing. Furthermore, our results confirm the substitution of leasing and debt financing for lessee firms. However, we find no evidence that firms use leasing as an instrument to reduce their tax burdens. Keywords: Leasing; financial constraints; capital structure; asymmetric information.
In this paper we investigate the comparative properties of empirically-estimated monetary models of the U.S. economy. We make use of a new data base of models designed for such investigations. We focus on three representative models: the Christiano, Eichenbaum, Evans (2005) model, the Smets and Wouters (2007) model, and the Taylor (1993a) model. Although the three models differ in terms of structure, estimation method, sample period, and data vintage, we find surprisingly similar economic impacts of unanticipated changes in the federal funds rate. However, the optimal monetary policy responses to other sources of economic fluctuations are widely different in the different models. We show that simple optimal policy rules that respond to the growth rate of output and smooth the interest rate are not robust. In contrast, policy rules with no interest rate smoothing and no response to the growth rate, as distinct from the level, of output are more robust. Robustness can be improved further by optimizing rules with respect to the average loss across the three models.
Renewed interest in fiscal policy has increased the use of quantitative models to evaluate policy. Because of modeling uncertainty, it is essential that policy evaluations be robust to alternative assumptions. We find that models currently being used in practice to evaluate fiscal policy stimulus proposals are not robust. Government spending multipliers in an alternative empirically-estimated and widely-cited new Keynesian model are much smaller than in these old Keynesian models; the estimated stimulus is extremely small with GDP and employment effects only one-sixth as large.
We examined the neural signatures of stimulus features in visual working memory (WM) by integrating functional magnetic resonance imaging (fMRI) and event-related potential data recorded during mental manipulation of colors, rotation angles, and color–angle conjunctions. The N200, negative slow wave, and P3b were modulated by the information content of WM, and an fMRI-constrained source model revealed a progression in neural activity from posterior visual areas to higher order areas in the ventral and dorsal processing streams. Color processing was associated with activity in inferior frontal gyrus during encoding and retrieval, whereas angle processing involved right parietal regions during the delay interval. WM for color–angle conjunctions did not involve any additional neural processes. The finding that different patterns of brain activity underlie WM for color and spatial information is consistent with ideas that the ventral/dorsal “what/where” segregation of perceptual processing influences WM organization. The absence of characteristic signatures of conjunction-related brain activity, which was generally intermediate between the 2 single conditions, suggests that conjunction judgments are based on the coordinated activity of these 2 streams. Keywords: EEG, fMRI, source analysis, visual, working memory
We show that loanword adaptation can be understood entirely in terms of phonological and phonetic comprehension and production mechanisms in the first language. We provide explicit accounts of several loanword adaptation phenomena (in Korean) in terms of an Optimality-Theoretic grammar model with the same three levels of representation that are needed to describe L1 phonology: the underlying form, the phonological surface form, and the auditory-phonetic form. The model is bidirectional, i.e., the same constraints and rankings are used by the listener and by the speaker. These constraints and rankings are the same for L1 processing and loanword adaptation.
Experimental data shows that adult learners of an artificial language with a phonotactic restriction learned this restriction better when being trained on word types (e.g. when they were presented with 80 different words twice each) than when being trained on word tokens (e.g. when presented with 40 different words four times each) (Hamann & Ernestus submitted). These findings support Pierrehumbert’s (2003) observation that phonotactic co-occurrence restrictions are formed across lexical entries, since only lexical levels of representation can be sensitive to type frequencies.
The present study argues that variation across listeners in the perception of a non-native contrast is due to two factors: the listener-specic weighting of auditory dimensions and the listener-specic construction of new segmental representations. The interaction of both factors is shown to take place in the perception grammar, which can be modelled within an OT framework. These points are illustrated with the acquisition of the Dutch three-member labiodental contrast [V v f] by German learners of Dutch, focussing on four types of learners from the perception study by Hamann and Sennema (2005a).
The multiplicity fluctuations in A+A collisions at SPS and RHIC energies are studied within the HSD transport approach. We find a dominant role of the fluctuations in the nucleon participant number for the final fluctuations. In order to extract physical fluctuations one should decrease the fluctuations in the participants number. This can be done considering very central collisions. The system size dependence of the multiplicity fluctuations in central A+A collisions at the SPS energy range – obtained in the HSD and UrQMD transport models – is presented. The results can be used as a ‘background’ for experimental measurements of fluctuations as a signal of the critical point. Event-by-event fluctuations of the K/p , K/p and p/p ratios in A+A collisions are also studied. Event-by-event fluctuations of the kaon to pion number ratio in nucleus-nucleus collisions are studied for SPS and RHIC energies. We find that the HSD model can qualitatively reproduce the measured excitation function for the K/p ratio fluctuations in central Au+Au (or Pb+Pb) collisions from low SPS up to top RHIC energies. The forward-backward correlation coefficient measured by the STAR Collaboration in Au+Au collisions at RHIC is also studied. We discuss the effects of initial collision geometry and centrality bin definition on correlations in nucleus-nucleus collisions. We argue that a study of the dependence of correlations on the centrality bin definition as well as the bin size may distinguish between these ‘trivial’ correlations and correlations arising from ‘new physics’. 5th International Workshop on Critical Point and Onset of Deconfinement - CPOD 2009, June 08 - 12 2009 Brookhaven National Laboratory, Long Island, New York, USA
This paper analyzes the risk properties of typical asset-backed securities (ABS), like CDOs or MBS, relying on a model with both macroeconomic and idiosyncratic components. The examined properties include expected loss, loss given default, and macro factor dependencies. Using a two-dimensional loss decomposition as a new metric, the risk properties of individual ABS tranches can directly be compared to those of corporate bonds, within and across rating classes. By applying Monte Carlo Simulation, we find that the risk properties of ABS differ significantly and systematically from those of straight bonds with the same rating. In particular, loss given default, the sensitivities to macroeconomic risk, and model risk differ greatly between instruments. Our findings have implications for understanding the credit crisis and for policy making. On an economic level, our analysis suggests a new explanation for the observed rating inflation in structured finance markets during the pre-crisis period 2004-2007. On a policy level, our findings call for a termination of the 'one-size-fits-all' approach to the rating methodology for fixed income instruments, requiring an own rating methodology for structured finance instruments. JEL Classification: G21, G28 Keywords: credit risk, risk transfer, systematic risk
The genus Haroldiataenius Chalumeau, 1981 (Aphodiinae: Eupariini) from southern United States, Mexico, and Central America is revised and nine species are recognized. The subgeneric name Sayloria Chalumeau, 1981 is synonymized with Haroldiataenius (sensu stricto) and Ataenius sabinoi Cartwright, 1974 is synonymized with A. lucanus Horn, 1871. Five species are transferred to Haroldiataenius from the genus Ataenius Harold creating the following new combinations: H. convexus (Robinson), H. griffini (Cartwright), H. lucanus (Horn), H. saramari (Cartwright), and H. semipilosus (Van Dyke). One new species,Haroldiataenius buvexus is described from Texas, USA. A key to species of Haroldiataenius is included and pertinent morphological details are illustrated.
The New World euparine scarab genera Parataenius Balthasar, 1961 and Pseudataenius Brown, 1927 are revised. Ataenius brunneus Schmidt is transferred to the genus Parataenius becoming Parataenius brunneus (Schmidt), new combination. The monospecific genus Ataenioides Petrovitz, 1973, is synonymized with Pseudataenius Brown, 1927, (new synonymy) and the type species, Ataenioides gracilitarsis Petrovitz, is given the new combination Pseudataenius gracilitarsis (Petrovitz). New species of Parataenius are described from southern South America: Parataenius selvae, P. estero, and P. martinezi. Keys for species of both genera are presented and pertinent morphological details are illustrated.
Epidermal growth factor (EGF) receptor belongs to the broad family of enzymatic receptors called receptor tyrosine kinases (RTKs). Generally, the binding of a ligand to these receptors leads to activation of their intracellular kinase activity that sets in motion a cascade of signaling events. In order to ensure appropriate responses to physiological stimuli, the cell is endowed with the ability to regulate signal transduction via numerous mechanisms such as dephosphorylation of the RTK and its substrates as well as downregulation of the RTK. Activation of EGFR is a potent mitogenic (proliferative) and motogenic (cell motility) signal that plays crucial roles during embryonic development and maintenance of adult tissue. EGFR signaling is primarily regulated by ligand-induced receptor internalization with subsequent degradation in lysosomes. While the complex of proteins that are recruited to EGFR after its activation is well understood, proteins that interact with the receptor in the absence of ligand binding are still not systematically studied. With the goal of identifying novel binding partners of non-activated EGFR, a membrane based yeast-two hybrid screen (MYTH) was conducted. MYTH is based on the principle of in vivo reconstitution of the N-terminus (Nub) and C-terminus (Cub) halves of ubiquitin once brought into close proximity. A chimeric protein consisting of EGFR fused to Cub and a transcription factor was used as a bait to screen Nub-tagged cDNA library. Analysis of resultant yeast transformants revealed a total of 87 proteins to interact with EGFR. Of these only 11 were previously shown to bind to EGFR. A majority of the other proteins were shown to interact with the receptor by yeast retransformation. Fifteen were confirmed to bind to EGFR by coimmunoprecipitation assays in mammalian cells. One of the novel EGFR interactors identified in the screen was histone deacetylase 6 (HDAC6). This deacetylase is localized in the cytoplasm and known to deacetylate alpha-tubulin, HSP90 and cortactin. The juxtamembrane region of EGFR binds to the Cterminus of HDAC6. Functionally, overexpression of wild type HDAC6 stabilized ligand-induced degradation of the receptor. On the other hand, deacetylase deficient or EGFR binding compromised mutants of HDAC6 were able to stabilize EGFR only partially. Downmodulation of HDAC6 expression by RNAi markedly accelerated degradation of the receptor. Taken together, HDAC6 is a negative regulator of EGFR downregulation that is dependent on its deacetylase activity and ability to bind to the receptor. Imaging studies revealed that HDAC6 does not affect internalization of EGFR from the plasma membrane but rather influences the post-endocytic trafficking of the receptor-ligand complex to lysosomes. Pulse-chase experiments using fluorophoretagged EGF showed that EGFR is transported faster towards the peri-nuclear region and delivered to late endosomes rapidly in HDAC6 depleted cells. HDAC6 is demonstrated to act, at least partly, by regulating the acetylation of alpha-tubulin. Upon EGFR activation, acetylation of alpha-tubulin on lysine 40 is progressively increased as shown by mass spectrometry and immunoblotting. Forced expression of a dominant negative mutant of alpha-tubulin, but not wild type alpha-tubulin, led to reduced speed and processive movement of early endosomes in GFP-Rab5 expressing cells. In a surprising twist, EGFR is able to phosphorylate HDAC6 on Tyr570. Phosphorylation of Tyr570 and Ser568 leads to inactivation of the deacetylase function of HDAC6 as shown by in vivo and in vitro assays. In summary, HDAC6 diminishes EGFR downregulation by slowing the transport of intracellular vesicles. The inhibitory effect is removed once HDAC6 is phosphorylated on key residues. In line with these findings, two recent reports have shown that hyper-acetylation of alpha-tubulin induced by inhibition of HDAC6 increases the transport of brain derived neurotrophic factor and JNK interacting protein-1 in different cell systems. Acetylated microtubules are more efficient in recruiting motor proteins like kinesin-1 and dynein. These findings indicate that HDAC6 plays an important regulatory role in intracellular trafficking pathways. However, several outstanding issues still remain unresolved. How does acetylation of microtubules influence vesicular trafficking? In this regard, the temporal and spatial dynamics of alpha-tubulin acetylation following EGFR activation should be studied. Furthermore, whether HDAC6 affects the trafficking of other endocytic cargos and additional organelles is an interesting question to address.
The selection of features for classification, clustering and approximation is an important task in pattern recognition, data mining and soft computing. For real-valued features, this contribution shows how feature selection for a high number of features can be implemented using mutual in-formation. Especially, the common problem for mutual information computation of computing joint probabilities for many dimensions using only a few samples is treated by using the Rènyi mutual information of order two as computational base. For this, the Grassberger-Takens corre-lation integral is used which was developed for estimating probability densities in chaos theory. Additionally, an adaptive procedure for computing the hypercube size is introduced and for real world applications, the treatment of missing values is included. The computation procedure is accelerated by exploiting the ranking of the set of real feature values especially for the example of time series. As example, a small blackbox-glassbox example shows how the relevant features and their time lags are determined in the time series even if the input feature time series determine nonlinearly the output. A more realistic example from chemical industry shows that this enables a better ap-proximation of the input-output mapping than the best neural network approach developed for an international contest. By the computationally efficient implementation, mutual information becomes an attractive tool for feature selection even for a high number of real-valued features.