Medium-Enhanced cc[over ¯] Radiation.

We show that the same QCD formalism that accounts for the suppression of high-p_{T} hadron and jet spectra in heavy-ion collisions predicts medium-enhanced production of cc[over ¯] pairs in jets. We demonstrate that this phenomenon, which cannot be accessed by traditional jet-quenching observables, can be directly observed using D^{0}D[over ¯]^{0}-tagged jets in nuclear collisions.

Discovering Partonic Rescattering in Light Nucleus Collisions.

We demonstrate that oxygen-oxygen collisions at the LHC provide unprecedented sensitivity to parton energy loss in a system whose size is comparable to those created in very peripheral heavy-ion collisions. With leading and next-to-leading order calculations of nuclear modification factors, we show that the baseline in the absence of partonic rescattering is known with up to 2% theoretical accuracy in inclusive oxygen-oxygen collisions. Surprisingly, a Z-boson normalized nuclear modification factor does not lead to higher theoretical accuracy within current uncertainties of nuclear parton distribution functions. We study a broad range of parton energy loss models and we find that the expected signal of partonic rescattering can be disentangled from the baseline by measuring charged hadron spectra in the range 20 GeV

Early- and Late-Time Behavior of Attractors in Heavy-Ion Collisions.

Whether, how, and to what extent solutions of Bjorken-expanding systems become insensitive to aspects of their initial conditions is of importance for heavy-ion collisions. Here we study 1+1D and phenomenologically relevant boost-invariant 3+1D systems in which initial conditions approach a universal attractor. In Israel-Stewart theory (IS) and kinetic theory where the universal attractor extends to arbitrarily early times, we show that all initial conditions approach the attractor at early times by a power law while their approach is exponential at late times. In these theories, the physical mechanisms of hydrodynamization operational at late times do not drive the approach to the attractor at early times, and the early-time attractor is reached prior to hydrodynamization. In marked contrast, the attractor in strongly coupled systems is realized concurrent with hydrodynamization. This qualitative difference may offer a basis for discriminating weakly and strongly coupled scenarios of heavy-ion collisions.

Accelerating cosmological expansion from shear and bulk viscosity.

The dissipation of energy from local velocity perturbations in the cosmological fluid affects the time evolution of spatially averaged fluid dynamic fields and the cosmological solution of Einstein's field equations. We show how this backreaction effect depends on shear and bulk viscosity and other material properties of the dark sector, as well as the spectrum of perturbations. If sufficiently large, this effect could account for the acceleration of the cosmological expansion.

Eccentricity fluctuations make flow measurable in high multiplicity p-p collisions.

Elliptic flow is a hallmark of collectivity in hadronic collisions. Its measurement relies on analysis techniques which require high event multiplicity and so far can only be applied to heavy ion collisions. Here, we delineate the conditions under which elliptic flow becomes measurable in the samples of high-multiplicity (dN(ch)/dy > or = 50) p-p collisions, which will soon be collected at the LHC. We observe that fluctuations in the p-p interaction region can result in a sizable spatial eccentricity even for the most central p-p collisions. Under relatively mild assumptions on the nature of such fluctuations and on the eccentricity scaling of elliptic flow, we find that the resulting elliptic flow signal in high-multiplicity p-p collisions at the LHC becomes measurable with standard techniques.

Local Monte Carlo implementation of the non-Abelian Landau-Pomeranschuk-Migdal effect.

The non-Abelian Landau-Pomeranschuk-Migdal (LPM) effect arises from the quantum interference between spatially separated, inelastic radiation processes in matter. A consistent probabilistic implementation of this LPM effect is a prerequisite for extending the use of Monte Carlo (MC) event generators to the simulation of jetlike multiparticle final states in nuclear collisions. Here, we propose a local MC algorithm, which is based solely on relating the LPM effect to the probabilistic concept of formation time for virtual quanta. This accounts probabilistically for the characteristic L2 dependence of average parton energy loss and the characteristic 1/square root(omega) modification of the non-Abelian LPM effect. Additional kinematic constraints are found to modify these L2 and omega dependencies characteristically in accordance with analytical estimates.

Anti-de sitter/conformal-field-theory calculation of screening in a hot wind.

One of the challenges in relating experimental measurements of the suppression in the number of J/psi mesons produced in heavy ion collisions to lattice QCD calculations is that whereas the lattice calculations treat J/psi mesons at rest, in a heavy ion collision a cc[over ] pair can have a significant velocity with respect to the hot fluid produced in the collision. The putative J/psi finds itself in a hot wind. We present the first rigorous nonperturbative calculation of the consequences of a wind velocity v on the screening length L(s) for a heavy quark-antiquark pair in hot N=4 supersymmetric QCD. We find L(s)(v,T)=f(v)[1-v(2)](1/4)/piT with f(v) only mildly dependent on v and the wind direction. This L(s)(v,T) approximately L(s)(0,T)/sqrt[gamma] velocity scaling, if realized in QCD, provides a significant additional source of J/psi suppression at transverse momenta which are high but within experimental reach.

Implications for molecular mechanisms of glycoprotein hormone receptors using a new sequence-structure-function analysis resource.

Comparison between wild-type and mutated glycoprotein hormone receptors (GPHRs), TSH receptor, FSH receptor, and LH-chorionic gonadotropin receptor is established to identify determinants involved in molecular activation mechanism. The basic aims of the current work are 1) the discrimination of receptor phenotypes according to the differences between activity states they represent, 2) the assignment of classified phenotypes to three-dimensional structural positions to reveal 3) functional-structural hot spots and 4) interrelations between determinants that are responsible for corresponding activity states. Because it is hard to survey the vast amount of pathogenic and site-directed mutations at GPHRs and to improve an almost isolated consideration of individual point mutations, we present a system for systematic and diversified sequence-structure-function analysis (http://www.fmp-berlin.de/ssfa). To combine all mutagenesis data into one set, we converted the functional data into unified scaled values. This at least enables their comparison in a rough classification manner. In this study we describe the compiled data set and a wide spectrum of functions for user-driven searches and classification of receptor functionalities such as cell surface expression, maximum of hormone binding capability, and basal as well as hormone-induced Galphas/Galphaq mediated cAMP/inositol phosphate accumulation. Complementary to known databases, our data set and bioinformatics tools allow functional and biochemical specificities to be linked with spatial features to reveal concealed structure-function relationships by a semiquantitative analysis. A comprehensive discrimination of specificities of pathogenic mutations and in vitro mutant phenotypes and their relation to signaling mechanisms of GPHRs demonstrates the utility of sequence-structure-function analysis. Moreover, new interrelations of determinants important for selective G protein-mediated activation of GPHRs are resumed.

Calculating the jet quenching parameter.

Models of medium-induced radiative parton energy loss account for the strong suppression of high-p(T) hadron spectra in square root of (S)NN=200 GeV Au-Au collisions at BNL RHIC in terms of a single "jet quenching parameter" q. We observe that q can be given a model-independent, nonperturbative, quantum field theoretic definition in terms of the short-distance behavior of a particular lightlike Wilson loop. We then use the anti-de Sitter/conformal-field-theory correspondence to obtain a strong-coupling calculation of q in hot N=4 supersymmetric QCD, finding q(SYM)=26.69 square root of alpha(SYM)N(c)T(3) in the limit in which both N(c) and 4pialpha(SYM)N(c) are large. Thus, at strong coupling q is not proportional to the entropy density s, or to some "number density of scatterers" since, unlike the number of degrees of freedom, q does not grow like N(c)(2).

The solution structure of an N-terminally truncated version of the yeast CDC24p PB1 domain shows a different beta-sheet topology.

Phox and Bem1 (PB1) domains mediate protein-protein interactions via the formation of homo- or hetero-dimers. The C-terminal PB1 domain of yeast cell division cycle 24 (CDC24p), a guanine-nucleotide exchange factor involved in cell polarity establishment, is known to interact with the PB1 domain occurring in bud emergence MSB1 interacting 1 (BEM1p) during the regulation of the yeast budding process via its OPR/PC/AID (OPCA) motif. Here, we present the structure of an N-terminally truncated version of the Sc CDC24p PB1 domain. It shows a different topology of the beta-sheet than the long form. However, the C-terminal part of the structure shows the conserved PB1 domain features including the OPCA motif with a slight rearrangement of helix alpha1. Residues which are important for the heterodimerization with BEM1p are structurally preserved.

Structural basis for APPTPPPLPP peptide recognition by the FBP11WW1 domain.

WW domains are small protein-protein interaction modules that recognize proline-rich stretches in proteins. The class II tandem WW domains of the formin binding protein 11 (FBP11) recognize specifically proteins containing PPLPp motifs as present in the formins that are involved in limb and kidney development, and in the methyl-CpG-binding protein 2 (MeCP2), associated with the Rett syndrome. The interaction involves the specific recognition of a leucine side-chain. Here, we report on the novel structure of the complex formed by the FPB11WW1 domain and the formin fragment APPTPPPLPP revealing the specificity determinants of class II WW domains.

Relating high-energy Lepton-Hadron, proton-nucleus, and nucleus-nucleus collisions through geometric scaling.

A characteristic feature of small-x lepton-proton data from HERA is geometric scaling: the fact that in the region of small Bjorken variable x, x less, similar 0.01, all data can be described by a single variable Q(2)/Q(2)(s,p)(x), with all x dependence encoded in the so-called saturation momentum Q(s,p)(x). Here, we observe that the same scaling ansatz accounts for nuclear photoabsorption cross sections and favors the nuclear dependence Q(2)(s,A) proportional, variant A(alpha)Q(2)(s,p), alpha approximately 4/9. We then make the empirical finding that the same A dependence accounts for the centrality evolution of the multiplicities measured in Au+Au collisions at RHIC. It also allows one to parametrize the high-p(t) particle suppression in d+Au collisions at forward rapidities. If these geometric scaling properties have a common dynamical origin, then this A dependence of Q(2)(s,A) should emerge as a consequence of the underlying dynamical model.

COPS--cis/trans peptide bond conformation prediction of amino acids on the basis of secondary structure information.

UNLABELLED: COPS predicts for all 20 naturally occurring amino acids whether the peptide bond in a protein is in cis or trans conformation. The algorithm is based only on secondary structure information of amino acid triplets without considering the amino acid sequence information. Conformation parameters are derived from solved 3D structures deposited in the PDB and led to propensities based on modified Chou-Fasman parameters. COPS analyses amino acid triplets taking only their respective secondary structure into consideration and upon application of a set of rules utilizing the conformation parameters, the N-terminal peptide bond conformation of the middle residue is predicted. COPS was tested on a random selection of protein datasets. AVAILABILITY: The COPS program and further information are freely available from the FMP website at http://www.fmp-berlin.de/nmr/cops CONTACT: labudde@fmp-berlin.de.

Comparative structural and energetic analysis of WW domain-peptide interactions.

WW domains are small globular protein interaction modules found in a wide spectrum of proteins. They recognize their target proteins by binding specifically to short linear peptide motifs that are often proline-rich. To infer the determinants of the ligand binding propensities of WW domains, we analyzed 42 WW domains. We built models of the 3D structures of the WW domains and their peptide complexes by comparative modeling supplemented with experimental data from peptide library screens. The models provide new insights into the orientation and position of the peptide in structures of WW domain-peptide complexes that have not yet been determined experimentally. From a protein interaction property similarity analysis (PIPSA) of the WW domain structures, we show that electrostatic potential is a distinguishing feature of WW domains and we propose a structure-based classification of WW domains that expands the existent ligand-based classification scheme. Application of the comparative molecular field analysis (CoMFA), GRID/GOLPE and comparative binding energy (COMBINE) analysis methods permitted the derivation of quantitative structure-activity relationships (QSARs) that aid in identifying the specificity-determining residues within WW domains and their ligand-recognition motifs. Using these QSARs, a new group-specific sequence feature of WW domains that target arginine-containing peptides was identified. Finally, the QSAR models were applied to the design of a peptide to bind with greater affinity than the known binding peptide sequences of the yRSP5-1 WW domain. The prediction was verified experimentally, providing validation of the QSAR models and demonstrating the possibility of rationally improving peptide affinity for WW domains. The QSAR models may also be applied to the prediction of the specificity of WW domains with uncharacterized ligand-binding properties.

Quantification of PDZ domain specificity, prediction of ligand affinity and rational design of super-binding peptides.

Transient macromolecular complexes are often formed by protein-protein interaction domains (e.g. PDZ, SH2, SH3, WW) which recognize linear sequence motifs with in vitro affinities typically in the micromolar range. The analysis of the resulting interaction networks requires a quantification of domain specificity and selectivity towards all possible ligands with physiologically relevant affinity. As representative examples, we determined specificity as a function of ligand sequence-dependent affinity contributions by statistical analysis of peptide library screens for the AF6, ERBIN and SNA1 (alpha-1-syntrophin) PDZ domains. For this purpose, the three PDZ domains were first screened for binding with a peptide library comprising 6223 human C termini created by SPOT synthesis. Based on the detected ligand preferences, we designed focused peptide libraries (profile libraries). These libraries were used to quantify the affinity contributions of the four C-terminal ligand residues by means of ANOVA models (analysis of variance) relating the C-terminal ligand sequences to the corresponding dissociation constants. Our models agreed well with experimentally determined dissociation constants and allowed us to design super binding peptides. The latter were shown experimentally to bind to their cognate PDZ domains with the highest affinity. In addition, we determined structure-activity relationships and thereby rationalized the position-specific affinity contributions. Furthermore, we used the statistical models to predict the dissociation constants for the complete ligand sequence space and thus determined the specificity overlap for the three investigated PDZ domains (). Altogether, we present an efficient method for profiling protein-protein interaction domains that provides a biophysical picture of specificity and selectivity. This approach allows the rational design of functional experiments and provides a basis for simulating interaction networks in the field of systems biology.

Medium modification of jet shapes and jet multiplicities.

Medium-induced parton energy loss is widely considered to underlie the suppression of high-pt leading hadron spectra in square root sNN = 200 GeV Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). Its description implies a characteristic kt broadening of the subleading hadronic fragments associated with the hard parton. However, this latter effect is more difficult to measure and has remained elusive so far. Here, we discuss how it affects genuine jet observables, which are accessible at the Large Hadron Collider and possibly at RHIC. We find that the kt broadening of jet multiplicity distributions provides a very sensitive probe of the properties of dense QCD matter, whereas the sensitivity of jet energy distributions is much weaker. In particular, the sensitive kinematic range of jet multiplicity distributions is almost unaffected by the high multiplicity background.

Energy dependence of the Cronin effect from nonlinear QCD evolution.

The nonlinear evolution of dense partonic systems has been suggested as a novel physics mechanism relevant for the dynamics of p-A and A-A collisions at collider energies. Here we study to what extent the description of Cronin enhancement in the framework of this nonlinear evolution is consistent with the recent observation in sqrt[s]=200 GeV d-Au collisions at the Relativistic Heavy Ion Collider. We solve the Balitsky-Kovchegov evolution equation numerically for several initial conditions encoding Cronin enhancement. We find that the properly normalized nuclear gluon distribution is suppressed at all momenta relative to that of a single nucleon. For the resulting spectrum of produced gluons in p-A and A-A collisions, the nonlinear QCD evolution is unable to generate a Cronin-type enhancement, and it quickly erases any such enhancement which may be present at lower energies.

Measuring the collective flow with jets.

In nucleus-nucleus collisions, high-p(T) partons interact with a dense medium, which possesses strong collective flow components. Here, we demonstrate that the resulting medium-induced gluon radiation does not depend solely on the energy density of the medium, but also on the collective flow. Both components can be disentangled by the measurement of particle production associated with high-p(T) trigger particles, jetlike correlations, and jets. In particular, we show that flow effects lead to a characteristic breaking of the rotational symmetry of the average jet energy and jet multiplicity distribution in the eta x phi plane. We argue that data on the medium-induced broadening of jetlike particle correlations in Au + Au collisions at the Relativistic Heavy-Ion Collider may provide evidence for a significant distortion of parton fragmentation due to the longitudinal collective flow.

Timing of network synchronization by refractory mechanisms.

Even without active pacemaker mechanisms, temporally patterned synchronization of neural network activity can emerge spontaneously and is involved in neural development and information processing. Generation of spontaneous synchronization is thought to arise as an alternating sequence between a state of elevated excitation followed by a period of quiescence associated with neuronal and/or synaptic refractoriness. However, the cellular factors controlling recruitment and timing of synchronized events have remained difficult to specify, although the specific temporal pattern of spontaneous rhythmogenesis determines its impact on developmental processes. We studied spontaneous synchronization in a model of 600-1,000 integrate-and-fire neurons interconnected with a probability of 5-30%. One-third of neurons generated spontaneous discharges and provided a background of intrinsic activity to the network. The heterogeneity and random coupling of these neurons maintained this background activity asynchronous. Refractoriness was modeled either by use-dependent synaptic depression or by cellular afterhyperpolarization. In both cases, the recruitment of neurons into spontaneous synchronized discharges was determined by the interplay of refractory mechanisms with stochastic fluctuations in background activity. Subgroups of easily recruitable neurons served as amplifiers of these fluctuations, thereby initiating a cascade-like recruitment of neurons ("avalanche effect"). In contrast, timing depended on the precise implementation of neuronal refractoriness and synaptic connectivity. With synaptic depression, neuronal synchronization always occurred stochastically, whereas with cellular afterhyperpolarization, stochastic turned into periodic behavior with increasing synaptic strength. These results associate the type of refractory mechanism with the temporal statistics and the mechanism of synchronization, thereby providing a framework for differentiating between cellular mechanisms of spontaneous rhythmogenesis.

WW domain sequence activity relationships identified using ligand recognition propensities of 42 WW domains.

WW domains mediate protein-protein interactions in a number of different cellular functions by recognizing proline-containing peptide sequences. We determined peptide recognition propensities for 42 WW domains using NMR spectroscopy and peptide library screens. As potential ligands, we studied both model peptides and peptides based on naturally occurring sequences, including phosphorylated residues. Thirty-two WW domains were classified into six groups according to detected ligand recognition preferences for binding the motifs PPx(Y/poY), (p/phi)P(p,g)PPpR, (p/phi)PPRgpPp, PPLPp, (p/xi)PPPPP, and (poS/poT)P (motifs according to modified Seefeld Convention 2001). In addition to these distinct binding motifs, group-specific WW domain consensus sequences were identified. For PPxY-recognizing domains, phospho-tyrosine binding was also observed. Based on the sequences of the PPx(Y/poY)-specific group, a profile hidden Markov model was calculated and used to predict PPx(Y/poY)-recognition activity for WW domains, which were not assayed. PPx(Y/poY)-binding was found to be a common property of NEDD4-like ubiquitin ligases.