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The energies of, and transition probabilities involving, the ground-state rotation bands of Os186, Os188, and Os190 are compared with a diagonalized rotation-vibration theory in which vibrations are considered to three phonon order. Agreement even in the Os transition region is found to be excellent. The theory appears to be particularly successful in predicting two phonon states in Os190.
The rotation-vibration model and the hydrodynamic dipole-oscillation model are unified. A coupling between the dipole oscillations and the quadrupole vibrations is introduced in the adiabatic approximation. The dipole oscillations act as a "driving force" for the quadrupole vibrations and stabilize the intrinsic nucleus in a nonaxially symmetric equilibrium shape. The higher dipole resonance splits into two peaks separated by about 1.5-2 MeV. On top of the several giant resonances occur bands due to rotations and vibrations of the intrinsic nucleus. The dipole operator is established in terms of the collective coordinates and the γ-absorption cross section is derived. For the most important 1- levels the relative dipole excitation is estimated. It is found that some of the dipole strength of the higher giant resonance states is shared with those states in which one surface vibration quantum is excited in addition to the giant resonance.
Collisions of Si(14.5A GeV+Au are investigated in the relativistic-quantum-molecular-dynamics approach. The calculated pseudorapidity distributions for central collisions compare well with recent experimental data, indicating a large degree of nuclear stopping and thermalization. Nevertheless, nonequilibrium effects play an important role in such complex multihadron reactions: They lead to a strong enhancement of the total kaon production cross sections, in good agreement with the experimental data, without requiring the formation of a deconfined quark-gluon plasma.
Angular and energy distributions of fragments emitted from fast nucleus-nucleus collisions (Ne--> U at 250, 400, and 800 MeV/N) are calculated with use of nuclear fluid dynamics. A characteristic dependence of the energy spectra and angular distributions on the impact parameter is predicted. The preferential sideward emission of reaction fragments observed in the calculation for nearly central collisions seems to be supported by recent experimental data.
We present an analysis of high energy heavy ion collisions at intermediate impact parameters, using a two-dimensional fluid-dynamical model including shear and bulk viscosity, heat conduction, a realistic treatment of the nuclear binding, and an analysis of the final thermal emission of free nucleons. We find large collective momentum transfer to projectile and target residues (the highly inelastic bounce-off effect) and explosion of the hot compressed shock zones formed during the impact. As the calculated azimuthal dependence of energy spectra and angular distributions of emitted nucleons depends strongly on the coefficients of viscosity and thermal conductivity, future exclusive measurements may allow for an experimental determination of these transport coefficients. The importance of 4π measurements with full azimuthal information is pointed out.
Two-particle correlation data are presented for the reaction Ar (800 MeV/ nucleon) + Pb. The experimental results are analyzed in the nuclear fluid dynamical and in a linear cascade model. We demonstrate that the collective hydrodynamical correlations dominate the measured two-particle correlation function for the heavy system studied. We discuss the transition from the early stages of the reaction which are governed by few nucleon correlations, to the later stages with their macroscopic flow which can only be reached using heavy colliding systems. The sensitivity of the correlation data on the underlying compressional dissipative processes is analyzed.
The fluid dynamical model is used to study the reactions 20Ne+238U and 40Ar+40Ca at Elab=390 MeV/nucleon. The calculated double differential cross sections d²ð/dΩdE exhibit sidewards maxima in agreement with recent experimental data. The azimuthal dependence of the triple differential distributions, to be obtained from an event-by-event analysis of 4π; exclusive experiments, can yield deeper insight into the collision process: Jets of nuclear matter are predicted with a strongly impact-parameter-dependent thrust angle θjet(b). NUCLEAR REACTIONS Ar+Ca, Ne+U, Elab=393 MeV/nucleon, fluid dynamics with thermal breakup, double differential cross sections, azimuthal dependence of triple differential cross sections, event-by-event thrust analysis of 4π exclusive experiments.
Measurement of complex fragments and clues to the entropy production from 42-137-MeV/nucleon Ar + Au
(1983)
Intermediate-rapidity fragments with A=1-14 emitted from 42-137-MeV/nucleon Ar + Au have been measured. Evidence is presented that these fragments arise from a common moving source. Entropy values are extracted from the mass distributions by use of quantum statistical and Hauser-Feshbach theories. The extracted entropy values of S/A≈2-2.4 are much smaller than the values expected from measured deuteron-to-proton ratios, but are still considerably higher than theoretically predicted values.
Proton spectra have been calculated for the reaction 12C(85 MeV/nucleon) + 197Au using a three-dimensional hydrodynamical model with viscosity and thermal conductivity and final thermal breakup. The theoretical results are compared to recent data. It is shown that the predicted flow effects are not observable as a result of the impact parameter averaging inherent in the inclusive proton spectra. In contrast, angular distributions of medium mass nuclei (A>3) in nearly central collisions can provide signatures for flow effects.
The time dependent Hartree-Fock approximation is used to study the dynamical formation of long-lived superheavy nuclear complexes. The effects of long-range Coulomb polarization are treated in terms of a classical quadrupole polarization model. Our calculations show the existence of "resonantlike" structures over a narrow range of bombarding energies near the Coulomb barrier. Calculations of 238U + 238U are presented and the consequences of these results for supercritical positron emission are discussed. NUCLEAR REACTIONS 238U + 238U collisions as a function of bombarding energy, in the time-dependent Hartree-Fock approximation. Superheavy molecules and strongly damped collisions.
Energy spectra for p, d, t, 3He, 4He, and 6He from the reaction 12C+197Au at 35 MeV/nucleon are presented. A common intermediate rapidity source is identified using a moving source fit to the spectra that yields cross sections which are compared to analogous data at other bombarding energies and to several different models. The excitation function of the composite to proton ratios is compared with quantum statistical, hydrodynamic, and thermal models.
Microscopic calculations of collective flow probing the short-range nature of the nuclear force
(1984)
Collisions between two nuclei have been modeled by numerical solution of classical approximations to the equations of motion of the constituent nucleons. For the reaction Nb(400 MeV/u)+Nb, a correlated sidewards emission of nucleons is observed. This is attributed to the repulsive short-range component of the nucleon-nucleon potential. A strong dependence of the flow angle on the impact parameter is observed, in accord with recent experimental results.
Rapidity dependence of entropy production in proton- and nucleus-induced reactions on heavy nuclei
(1984)
The entropy of hot nuclear systems is deduced from the mass distribution of fragments emitted from high energy proton- and nucleus-induced reactions via a quantum statistical model. It is found that the entropy per baryon, S/A, of intermediate rapidity ("participant") fragments is higher than the entropy of target rapidity ("spectator") fragments. The spectator fragments exhibit S/A values of ≅ 1.8 independent of the projectile energy from 30 MeV/nucleon up to 350 GeV. This value of the entropy coincides with the entropy at which nuclear matter becomes unbound.
Kinetic energy flow in Nb(400 A MeV) + Nb: evidence for hydrodynamic compression of nuclear matter
(1984)
A kinetic-energy—flow analysis of multiplicity-selected collisions of 93Nb(Elab=400A MeV)+93Nb is performed on the basis of the nuclear fluid dynamical model. The effects of finite particle numbers on the flow tensor are explicitly taken into account. Strong sidewards peaks are predicted in dN/dcosθF, the distribution of event by event flow angles. This is in qualitative agreement with recent data from the "Plastic Ball" electronic detection system. Cascade simulations fail to reproduce the data.
Nuclear collisions from 0.3 to 2 GeV/nucleon are studied in a microscopic theory based on Vlasov's self-consistent mean field and Uehling-Uhlenbeck's two-body collision term which respects the Pauli principle. The theory explains simultaneously the observed collective flow and the pion multiplicity and gives their dependence on the nuclear equation of state.
The novel momentum analysis technique introduced by Danielewicz and Odyniec can be used to detect and exhibit collective flow in the light system Ar(1800 MeV/nucleon) + KCl where the usual kinetic energy flow analysis fails. The microscopic Vlasov-Uehling-Uhlenbeck theory which includes the nuclear mean field, two-body collisions, and Pauli blocking is used to study this phenomenon. The resulting transverse momentum transfers turn out to be quite sensitive to the nuclear equation of state. From a comparison with experimental data, evidence is presented for a rather stiff nuclear equation of state. The cascade model is unable to describe the data.
The role of nonequilibrium and quantal effects in fast nucleus-nucleus collisions is studied via the Vlasov-Uehling-Uhlenbeck theory which includes the nuclear mean field dynamics, two-body collisions, and Pauli blocking. The intranuclear cascade model, where the dynamics is governed by independent NN collisions, and the Vlasov equation, where the nuclear mean field determines the collision dynamics, are also studied as reference cases. The Vlasov equation (no collision term) yields single particle distribution functions which–after the reaction–are only slightly modified in momentum space; even in central collisions, transparency is predicted. This is in agreement with the predictions of the quantal time-dependent Hartree-Fock method. In contrast, large momentum transfer is obtained when the Uehling-Uhlenbeck collision term is incorporated; then the final momentum distribution is nearly spherically symmetric in the center of mass and a well-equilibrated nuclear system is formed: the nuclei stop each other; the translational kinetic energy is transformed into randomized microscopic motion. The Vlasov-Uehling-Uhlenbeck theory is supplemented with a phase space coalescence model of fragment formation. Calculated proton spectra compare well with recent data for Ar(42, 92, and 137 MeV/nucleon) + Ca. Also the total yields of medium mass fragments are well reproduced in the present approach. The mean field dynamics without two-body collisions, on the other hand, exhibits forward peaked proton distributions, in contrast to the data. The cascade approach underpredicts the yields of low energy protons by more than an order of magnitude.
The influence of fluctuations of the shape degree of freedom in collisions of deformed nuclei with energies between 0.8 and 2.1 GeV/nucleon is analyzed on the basis of an intranuclear cascade simulation for the strongly deformed systems 46Ti+ 46Ti and 166Er+ 166Er. While there is a considerable sensitivity of the global event variables to the orientation for polarized beams and targets, this dependence disappears in the average over all orientations for impact parameter selected and integrated events. The dependence of the nuclear stopping and thermalization on the size of the system under consideration and on the bombarding energy is also investigated.
We study the recent claim that the intranuclear cascade model exhibits collective sidewards flow. 4000 intranuclear cascade simulations of the reaction Nb(400 MeV/nucleon)+Nb are performed employing bound and unbound versions of the Cugnon cascade. We show that instability of the target and projectile nuclei in the unbound cascade produces substantial spurious sidewards flow angles, for spectators as well as for participants. Once the nuclear binding is included, the peak of the flow angle distributions for the participants alone is reduced from 35° to 17°. The theoretical ‘‘data’’ are subjected to the experimental multiplicity and efficiency cuts of the plastic ball 4π electronic spectrometer system. The flow angular distributions obtained from the bound cascade—with spectators and participants subjected to the plastic ball filter—are forward peaked, in contrast to the plastic ball data. We discuss the uncertainties encountered with the application of the experimental efficiency and multiplicity filter. The influence of the Pauli principle on the flow is also discussed. The lack of flow effects in the cascade model clearly reflects the absence of the nuclear compression energy that can cause substantially larger collective sidewards motion—there is too little intrinsic pressure built up in the cascade model.
Time dependent dirac equation with relativistic mean field dynamics applied to heavy ion scattering
(1986)
We treat the relativistic propagation of nucleons coupled to scalar- and vector-meson fields in a mean-field approximation. The time-dependent Dirac and mean-meson-field equations are solved numerically in three dimensions. Collisions of 16O(300, 600, and 1200 MeV/nucleon) + 16O are studied for various impact parameters. The results are compared to other recent theoretical approaches. The calculations predict spallation, large transverse-momentum transfer, and positive-angle sidewards flow, in qualitative agreement with the data in this energy regime.
Studying Walecka's mean-field theory we find that one can reproduce the observed binding energy and density of nuclear matter within experimental precision in an area characterized by a line in the coupling-constant plane. A part of this line defines systems which exhibit a phase transition around Tc~200 MeV for zero baryon density. The rest corresponds to such systems where the phase transition is absent; in that case a peak appears in the specific heat around T~200 MeV. We interpret these results as indicating that the hadron phase of nuclear matter alone indicates the occurrence of an abrupt change in the bulk properties around ρV~0 and T~200 MeV.
We present a theoretical description of nuclear collisions which consists of a three-dimensional fluid-dynamical model, a chemical equilibrium breakup calculation for local light fragment (i.e., p, n, d, t, 3He, and 4He) production, and a final thermal evaporation of these particles. The light fragment cross sections and some properties of the heavy target residues are calculated for the asymmetric system Ne+U at 400 MeV/N. The results of the model calculations are compared with recent experimental data. Several observable signatures of the collective hydrodynamical processes are consistent with the present data. An event-by-event analysis of the flow patterns of the various clusters is proposed which can yield deeper insight into the collision dynamics.
Intranuclear cascade calculations and fluid dynamical predictions of the kinetic energy flow are compared for collisions of 40Ca + 40Ca and 238U + 238U. The aspect ratio, R13, as obtained from the global analysis, is independent of the bombarding energy for the intranuclear cascade model. Fluid dynamics, on the other hand, predicts a dramatic increase of R13 at medium energies Elab≲200 MeV/nucleon. In fact, R13(Elab) directly reflects the incompressibility of the nuclear matter and can be used to extract the nuclear equation of stat at high densities. Distortions of the flow tensor due to few nucleon scattering are analyzed. Possible procedures to remove this background from experimental data are discussed.
We analyze the phase structure of the nonlinear mean-field meson theory of baryonic matter (nucleons plus delta resonances). Depending on the choice of the coupling constants, we find three physically distinct phase transitions in this theory: a nucleonic liquid-gas transition in the low temperature, Tc<20 MeV, low density, ρ≃0.5ρ0, regime, a high-temperature (T≃150 MeV) finite density transition from a gas of massive hadrons to a nearly massless baryon, antibaryon plasma, and, third, a strong phase transition from the nucleonic fluid to a resonance-dominated ‘‘delta-matter’’ isomer at ρ>2ρ0 and Tc<50 MeV. All three phase transitions are of first order. It is shown that the occurrence of these different phase transitions depends critically on the coupling constants. Since the production of pions also depends strongly on the coupling constants, it is seen that the equation of state cannot be derived unambiguously from pion data.
We study the dynamics of high energy heavy ion collisions through the Vlasov-Uehling-Uhlenbeck approach. Equilibration is observed, for central collisions. It is shown that the produced entropy, the pion multiplicity, flow angle, and transverse momentum distributions saturate at the moment of maximum compression and temperature. The effects of the nuclear equation of state and the Pauli principle are investigated. For the flow angle distribution there is a 20 deg reduction of the peak flow angle due to the Pauli principle. A stiff equation of state results in a 10–20 deg increase over the soft equation of state at all energies. The transverse momentum at projectile rapidity exhibits a peak structure as a function of impact parameter b. A 40% difference between soft and hard equation of state is observed for the peak impact parameter, i.e., for intermediate multiplicities.
The final states of central Ca + Ca and Nb + Nb collisions at 400 and 1050 MeV/nucleon and at 400 and 650 MeV/nucleon, respectively, are studied with two independently developed statistical models, namely the classical microcanonical model and the quantum-statistical grand canonical model. It is shown that these models are in agreement with each other for these systems. Furthermore, it is demonstrated that there is essentially a one-to-one relationship between the observed relative abundances of the light fragments p, d, t, 3He, and α and the entropy per nucleon, for breakup temperatures greater than 30 MeV. Entropy values of 3.5–4 are deduced from high-multiplicity selected fragment yield data.
We demonstrate that momentum-dependent nuclear interactions (MDI) have a large effect on the dynamics and on the observables of high-energy heavy-ion collisions: A soft potential with MDI suppresses pion and kaon yields much more strongly than a local hard potential and results in transverse momenta intermediate between soft and hard local potentials. The collective-flow angles and the deuteron-to-proton ratios are rather insensitive to the MDI. Only simultaneous measurements of these observables can give clues on the nuclear equation of state at densities of interest for supernova collapse and neutron-star stability.
The recent attempts to extract the temperature in the late stage of medium energy (20–60 MeV/nucleon) heavy ion collisions from the yields of γ- and particle-instable fragments are discussed. The quantum statistical model is employed to demonstrate that feeding from instable states distorts the yields used for the temperature determination severely. Some particle instable fragments are only moderately affected by feeding. These selected species can still be useful for determining the temperature. The breakup temperatures of the fragment conglomerate extracted with this method are T≃4–8 MeV, much smaller than the corresponding slope factors, which indicate T∼15 MeV.
Introduction: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. Methods: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. Results: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. Conclusion: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.
Background Fermentation of lignocellulosic biomass is an attractive alternative for the production of bioethanol. Traditionally, the yeast Saccharomyces cerevisiae is used in industrial ethanol fermentations. However, S. cerevisiae is naturally not able to ferment the pentose sugars D-xylose and L-arabinose, which are present in high amounts in lignocellulosic raw materials. Results We describe the engineering of laboratory and industrial S. cerevisiae strains to co-ferment the pentose sugars D-xylose and L-arabinose. Introduction of a fungal xylose and a bacterial arabinose pathway resulted in strains able to grow on both pentose sugars. Introduction of a xylose pathway into an arabinose-fermenting laboratory strain resulted in nearly complete conversion of arabinose into arabitol due to the L-arabinose reductase activity of the xylose reductase. The industrial strain displayed lower arabitol yield and increased ethanol yield from xylose and arabinose. Conclusion Our work demonstrates simultaneous co-utilization of xylose and arabinose in recombinant strains of S. cerevisiae. In addition, the co-utilization of arabinose together with xylose significantly reduced formation of the by-product xylitol, which contributed to improved ethanol production.
We study effects of the mean field in hot compressed nuclear matter in the context of the Vlasov Uehling-Uhlenbeck theory. The expansion of a spherical distribution at different temperatures is studied along with collisions of Nb+Nb and Au+Au at lab energies from 50 to 1050 MeV/nucleon. In both the expansion and the actual heavy ion collision simulation, a transition behavior is seen only at the lowest temperature (T<10 MeV) or bombarding energy (E=50 MeV/nucleon), where the attractive part of the mean field is able to bind the expanding matter. At the lowest energy one thus sees the formation of a central residue, whereas at higher bombarding energies there is complete disintegration of the centrally colliding nuclei. The spectrum of emitted nucleons is found to be much hotter than the kinetic energy spectrum of the central emitting region. The extracted temperature slope parameters are in agreement with recent data.
Background: Particle Swarm Optimization (PSO) is an established method for parameter optimization. It represents a population-based adaptive optimization technique that is influenced by several "strategy parameters". Choosing reasonable parameter values for the PSO is crucial for its convergence behavior, and depends on the optimization task. We present a method for parameter meta-optimization based on PSO and its application to neural network training. The concept of the Optimized Particle Swarm Optimization (OPSO) is to optimize the free parameters of the PSO by having swarms within a swarm. We assessed the performance of the OPSO method on a set of five artificial fitness functions and compared it to the performance of two popular PSO implementations. Results: Our results indicate that PSO performance can be improved if meta-optimized parameter sets are applied. In addition, we could improve optimization speed and quality on the other PSO methods in the majority of our experiments. We applied the OPSO method to neural network training with the aim to build a quantitative model for predicting blood-brain barrier permeation of small organic molecules. On average, training time decreased by a factor of four and two in comparison to the other PSO methods, respectively. By applying the OPSO method, a prediction model showing good correlation with training-, test- and validation data was obtained. Conclusion: Optimizing the free parameters of the PSO method can result in performance gain. The OPSO approach yields parameter combinations improving overall optimization performance. Its conceptual simplicity makes implementing the method a straightforward task.
The existence of a mean-square continuous strong solution is established for vector-valued Itö stochastic differential equations with a discontinuous drift coefficient, which is an increasing function, and with a Lipschitz continuous diffusion coefficient. A scalar stochastic differential equation with the Heaviside function as its drift coefficient is considered as an example. Upper and lower solutions are used in the proof.
Streamer chamber data for collisions of Ar + KCl and Ar + BaI2 at 1.2 GeV/nucleon are compared with microscopic model predictions based on the Vlasov-Uehling-Uhlenbeck equation, for various density-dependent nuclear equations of state. Multiplicity distributions and inclusive rapidity and transverse momentum spectra are in good agreement. Rapidity spectra show evidence of being useful in determining whether the model uses the correct cross sections for binary collisions in the nuclear medium, and whether momentum-dependent interactions are correctly incorporated. Sideward flow results do not favor the same nuclear stiffness parameter at all multiplicities.
We demonstrate that strangeness separates in the Gibbs-phase coexistence between a baryon-rich quark-gluon plasma and hadron matter, even at T=0. For finite temperatures this is due to the associated production of kaons (containing s¯ quarks) in the hadron phase while s quarks remain in the deconfined phase. The s-s¯ separation results in a strong enhancement of the s-quark abundance in the quark phase. This mechanism is further supported by cooling and net strangeness enrichment due to the prefreezeout evaporation of pions and K+, K0, which carry away entropy and anti- strangeness from the system. Metastable droplets (i.e., stable as far as weak interactions are not regarded) of strange-quark matter (‘‘strangelets’’) can thus be formed during the phase transition. Such cool, compact, long-lived clusters could be experimentally observed by their unusually small Z/A ratio (≤0.1–0.3). Even if the strange-quark-matter phase is not stable under strong interactions, it should be observable by the delayed correlated emission of several hyperons. This would serve as a unique signature for the transient formation of a quark-gluon plasma.
We investigate the onset of multifragmentation employing an improved version of the N-body ‘‘quantum’’ molecular-dynamics approach. We study in detail the reaction 18O+197Au at 84 MeV/nucleon and find good agreement between the calculated results and the data for the double-differential proton cross section, the mass yield, the multiplicity, the kinetic energy of the fragments, and even for the kinematic correlations between intermediate mass fragments (IMF’s), which have been measured in this experiment for the first time. We observe a strong correlation between the impact parameter and both the size of the target remnant as well as the average proton multiplicity. Hence both observables can be used to determine the impact parameter experimentally. The IMF’s come from the most central collisions. The calculations confirm the experimental result that they are not emitted from an equilibrated system. Although the inclusive energy spectra look thermal, we cannot identify an impact parameter-independent isotropically emitting source. Even in central collisions global equilibrium is not observed. We find that multifragment emission at this bombarding energy is caused by a process very similar to that proposed in the macroscopic cold multifragmentation model. Thus it has a different origin than at beam energies around 1 GeV/nucleon, although the mass yield has an almost identical slope.
We investigate the hydrodynamical flow of nuclear matter in a conical-shock-wave scenario of a central, asymmetric heavy-ion collision. This work is motivated by a suggestion of Chapline and Granik that the creation of a deconfined phase of quarks and gluons behind the shock will appreciably increase the deflection angle of the matter flow. We employ several hadron matter equations of state recently suggested to solve the conical-shock-wave problem and compare the results with a calculation using the bag equation of state. We find that large differences in the deflection angle obtained in the rest frame of the shock vanish in the laboratory system. However, a signature for the deconfinement transition may be the transverse momentum of the matter flow, which is up to a factor of 2 larger for the quark-gluon plasma. Thus, an excitation function of the mean transverse momentum would show an increase at a certain bombarding energy, signaling the onset of the deconfinement transition.
We study the transition from fusion-fission phenomena at about 20 MeV/nucleon multifragmentation at 100–200 MeV/nucleon in the reaction 16O+80Br employing the quantum molecular dynamics model. The time evolution of the density and mass distribution, the charged-particle multiplicity, and spectra as well as angular distributions of light particles are investigated. The results exhibit the transition of the disassembly mechanism, but no sharp change is found. The results are in good agreement with recently measured 4-Pi data.
Inclusive neutron spectra were measured at 0°, 4°, 8°, 15°, 30°, and 42° from Nb-Nb and Au-Au collisions at 800 MeV/nucleon. A peak that originates from neutron evaporation from the projectile appears in the spectra at angles out to 8°. The shapes and magnitudes of the spectra are compared with those calculated from models of nucleus-nucleus collisions. The differential cross sections for Au-Au collisions are about four times those for Nb-Nb collisions. The predictions of the Vlasov-Uehling-Uhlenbeck (VUU) and QMD theories agree with the angular distributions of the differential cross sections except at small angles; the VUU prediction overestimates the angular distributions from a few degrees to about 20°, whereas the QMD prediction underestimates the angular distributions below 8°. The Firestreak model overestimates the angular distribution for Nb-Nb collisions and underestimates it for Au-Au collisions. Also, the VUU and QMD models agree with the measured double-differential cross sections in more angular and energy regions than the Firestreak and intranuclear cascade models; however, none of the models can account for the peaks at small angles (θ≤15°).
Within a relativistic mean-field theory (RMFT) experimental data on the single-particle spectra of lambda hypernuclei are well reproduced. It is shown that the coupling constants cannot be fixed unambiguously from the single-particle spectra. The stability and structure of multi-lambda hypernuclei is explored on the basis of the RMFT using the coupling constants as determined from the observed single lambda hypernuclear levels. It is predicted that multistrange nuclei exhibit an enhanced interaction radius, which further increases in the case of finite temperatures. We suggest that multi-lambda hypernuclei could be produced in high-energy heavy ions and observed in secondary noncharge-changing reactions. The equation of state of lambda matter and the possibility of pure lambda droplets are also discussed.
Shock discontinuities around the confinement-deconfinement transition in baryon-rich dense matter
(1989)
Nuclear transport models are important tools for interpretation of many heavy-ion experiments and are essential in efforts to probe the nuclear equation of state. In order to fulfill these roles, the model predictions should at least agree with observed single-particle-inclusive momentum spectra; however, this agreement has recently been questioned. The present work compares the Vlasov-Uehling-Uhlenbeck model to data for mass-symmetric systems ranging from 12C+12C to 139La+139La, and we find good agreement within experimental uncertainties at 0.4A and 0.8A GeV. For currently available data, these uncertainties are too large to permit effective nucleon-nucleon scattering cross sections in the nuclear medium to be extracted at a useful level of precision.
Nuclear transport models including density- and momentum-dependent mean-field effects are compared to intranuclear-cascade models and tested on recent data on inclusive p-like cross sections for 800A-MeV La+La. We find a remarkable agreement between most model calculations but a systematic disagreement with the measured yield at 20°, possibly indicating a need for modification of nuclear transport properties at high densities.
The quantum molecular dynamic method is used to study multifragmentation and fragment flow and their dependence on in-medium cross sections, momentum dependent interactions, and the nuclear equation of state, for collisions of 197Au+197Au and 93Nb+93Nb in the bombarding energy regime from 100 to 800A MeV. Time and impact parameter dependence of the fragment formation and their implications for the conjectured liquid-vapor phase transition are investigated. We find that the inclusive fragment mass distribution is independent of the equation of state and exhibits a power-law behavior Y(A)∼A-τ with an exponent τ≊-2.3. True multifragmentation events are found in central collisions for energies Elab∼30–200 MeV/nucleon. The associated light fragment (d,t,α) to proton ratios increase with the multiplicity of charged particles and decrease with energy, in agreement with recent experiments. The calculated absolute charged particle multiplicities, the multiplicities of intermediate mass (A>4) fragments, and their respective rapidity distributions do compare well with recent 4π data, but are quite insensitive to the equation of state. On the other hand, these quantities depend sensitively on the nucleon-nucleon scattering cross section, and can be used to determine σ experimentally. The transverse momentum flow of the complex fragments increases with the stiffness of the equation of state. Reduced (in-medium) n-n scattering cross sections reduce the fragment flow. Momentum dependent interactions increase the fragment flow. It is shown that the measured fragment flow at 200A MeV can be reproduced in the model. We find that also the increase of the px/A values with the fragment mass is in agreement with experiments. The calculated fragment flow is too small as compared to the plastic ball data, if a soft equation of state with in-medium corrections (momentum dependent interactions plus reduced cross sections) is employed. An alternative, most intriguing resolution of the puzzle about the stiffness of the equation of state could be an increase of the scattering cross sections due to precritical scattering in the vicinity of a phase transition.
The statistical model is used to illustrate the consequences of a successive binary decay mechanism as the initial nuclear excitation is pushed towards the limits of stability. The partition of the excitation energy between light and heavy fragments is explicitly calculated, as are the consequences of the decay of the primary light fragments to particle-bound residual nuclei which would be observed experimentally. The test nucleus 100 44 Ru is considered at initial excitations of 100, 200, 400, and 800 MeV. Exit channels of n, p, and α; and 100 clusters of 3 ≤ Z ≤ 20 ≤ 4, 6 ≤ A ≤ 48 are considered from all nuclides in the deexcitation cascade. The total primary and final cluster yields are shown versus Z and initial excitation. The primary versus final yields are also shown individually for 12C, 26Mg, and 48Ca. We show how multifragmentation yields will change with the excitation energy due to a successive binary decay mechanism. Measurements that may be prone to misinterpretation are discussed, as are those that should be representative of initial nucleus excitation.
Distillation and survival of strange quark matter droplets in ultrarelativistic heavy ion collisions
(1991)
Recently it has been suggested that rather cold droplets of absolutely stable or metastable strange-quark matter may be distilled in heavy-ion collisions during the phase transition from a baryon-rich quark-gluon plasma (QGP) to hadron matter. Here we present a model describing the hadronization of the QGP through particle emission, which is based solely on thermodynamical arguments. Pions and K+’s and K0’s carry away entropy and antistrangeness from the system, thus facilitating the cooling process and the strangelet formation. Our results are supported by revised more sophisticated rate calculations. Two rather unexpected results are obtained when this model is applied to the investigation of strangelet production. The strangeness separation mechanism and the formation process works well even for higher initial entropies per baryon, tantamount to higher bombarding energies. The surviving strangelets have a rather high strangeness content, fs∼1.2–2 [i.e., Z/A∼(-0.1)–(-0.5)]. Hence droplets of strange-quark matter with a baryon number of ∼10–30 and with a negative charge may be produced. They may serve as a unique signature for the transient formation of a quark-gluon plasma in heavy-ion collisions.
Relativistic heavy ion collisions constitute a prolific source of hyperons: tens of hyperons per event are predicted at energies E≥10 GeV/nucleon, providing a scenario for the formation of metastable exotic multihypernuclear objects. They may exhibit exceptional properties: bound neutral (e.g., 4M2Λ2n, 10M2Λ8n, pure Λ droplets, 8Λ) and even negatively charged composites objects with positive baryon number (e.g., 4M2Σ-2n, 6M2Λ2Ξ-2n) could be formed in rare events. Such negative nuclei can easily be identified in a magnetic spectrometer. They could be considerably more abundant than antinuclei of the same A. We use the relativistic meson-baryon field theory—which gives an excellent description of normal nuclear and single-Λ hypernuclear properties—to calculate the rich spectrum of such exotic objects, their stability, and their structure. We also find solutions for a large variety of bound short-lived nuclei (e.g., 8M2Λ,2Σ-2p2n), which may decay strongly via formation of cascade (Ξ) particles. Multi-Ξ hypernuclei are also evaluated. A variety of potential candidates for such metastable exotic nuclei is presented. It turns out that the properties of such exotic multihypernuclear objects reveal quite similar features as the strangelet proposed as a unique signature for quark-gluon plasma formation in heavy ion collisions.
We present a new type of flow analysis, based on a particle-pair correlation function, in which there is no need for an event-by-event determination of the reaction plane. Consequently, the need to correct for dispersion in an estimated reaction plane does not arise. Our method also offers the option to avoid any influence from particle misidentification. Using this method, streamer chamber data for collisions of Ar+KCl and Ar+BaI2 at 1.2 GeV/nucleon are compared with predictions of a nuclear transport model.
A quasiclassical Pauli potential is used to simulate the Fermi motion of nucleons in a molecular dynamical simulation of heavy ion collisions. The thermostatic properties of a Fermi gas with and without interactions are presented. The inclusion of this Pauli potential into the quantum molecular dynamics (QMD) approach yields a model with well defined fermionic ground states, which is therefore also able to give the excitation energies of the emitted fragments. The deexcitation mechanisms (particle evaporation and multifragmentation) of the new model are investigated. The dynamics of the QMD with Pauli potential is tested by a wide range of comparisons of calculated and experimental double-differential cross sections for inclusive p-induced reactions at incident energies of 80 to 160 MeV. Results at 256 and 800 MeV incident proton energy are presented as predictions for completed experiments which are as yet unpublished.
Stopping power and thermalization in relativistic heavy ion collisions is investigated employing the quantum molecular dynamics approach. For heavy systems stopping of the incoming nuclei is predicted, independent of the energy. The influence of the quantum effects and their increasing importance at low energies, is demonstrated by inspection of the mean free path of the nucleons and the n-n collision number. Classical models, which neglect these effects, overestimate the stopping and the thermalization as well as the collective flow and squeeze out. The sensitivity of the transverse and longitudinal momentum transfer to the in-medium cross section and to the pressure is investigated.
Experimental results are presented on the charge, velocity, and angular distributions of intermediate mass fragments (IMFs) for the reaction Fe+Au at bombarding energies of 50 and 100 MeV/nucleon. Results are compared to the quantum molecular dynamics (QMD) model and a modified QMD which includes a Pauli potential and follows the subsequent statistical decay of excited reaction products. The more complete model gives a good representation of the data and suggests that the major source of IMFs at large angles is due to multifragmentation of the target residue.
Strange hadronic matter
(1993)
In an extended mean field theory, we find a large class of bound multistrange objects, formed from combinations of {p,n,Λ,Ξ0,Ξ-} baryons, which are stable against strong decay. We predict a maximal binding energy per baryon of EB/A≊-21 MeV, strangeness per baryon fs≊1.2, charge per baryon fq≊-0.1 to 0, and baryon density 2.5–3 times that of ordinary nuclei. For A≥6, we obtain stable combinations involving only {Λ,Ξ0,Ξ-} hyperons.
Strong correlations between baryon stopping in the projectile rapidity hemisphere and target excitation have been found in the light-ion-induced reactions at the BNL Alternating Gradient Synchrotron (AGS) (E814 group). Results in the framework of the relativistic molecular dynamics approach (RQMD) describe recent E814 data quite well. We discuss the RQMD results together with proton and pion data from the E802 group near midrapidity. They have raised the question of whether partial transparency could be seen in these experiments. The RQMD results indicate strong transverse baryon flow in central Si+Au collisions after the projectile has been stopped in the target.
We present a calculation of antiproton yields in Si+Al and Si+Au collisions at 14.5A GeV in the framework of the relativistic quantum molecular dynamics approach (RQMD). Multistep processes lead to the formation of high-mass flux tubes. Their decay dominates the initial antibaryon yield. However, the subsequent annihilation in the surrounding baryon-rich matter suppresses the antiproton yield considerably: Two-thirds of all antibaryons are annihilated even for the light Si+Al system. Comparisons with preliminary data of the E802 experiment support this analysis.
Accurate impact parameter determination in a heavy-ion collision is crucial for almost all further analysis. We investigate the capabilities of an artificial neural network in that respect. First results show that the neural network is capable of improving the accuracy of the impact parameter determination based on observables such as the flow angle, the average directed inplane transverse momentum and the difference between transverse and longitudinal momenta. However, further investigations are necessary to discover the full potential of the neural network approach.
Azimuthal correlations of pions are studied with the quantum molecular dynamics model. Pions are preferentially emitted perpendicular to the reaction plane. Our analysis shows that this anisotropy is dominated by pion absorption on the spectator matter in the reaction plane. Pions emitted perpendicular to the reaction plane undergo less rescattering than those emitted in the reaction plane and might therefore be more sensitive to the early hot and dense reaction phase.
We study dilepton production from a quark-gluon plasma of given energy density at finite quark chemical potential μ and find that the dilepton production rate is a strongly decreasing function of μ. Therefore, the signal to background ratio of dileptons from a plasma created in a heavy-ion collision may decrease significantly.
Viscous hydrodynamic calculations of high energy heavy-ion collisions (Nb-Nb and Au-Au) from 200 to 800 MeV/nucleon are presented. The resulting baryon rapidity distributions, the in-plane transverse momentum transfer (bounce-off), and the azimuthal dependence of the midrapidity particles (off-plane squeeze out) compare well with Plastic Ball data. We find that the considered observables are sensitive both to the nuclear equation of state and to the nuclear shear viscosity η. Transverse momentum distributions indicate a high shear viscosity (η≊60 MeV/fm2 c) in the compression zone, in agreement with nuclear matter estimates. The bulk viscosity ζ influences only the entropy production during the expansion stage; collective observables like flow and dN/dY do not depend strongly on ζ. The recently observed off-plane (φ=90°) squeeze-out, which is found in the triple-differential rapidity distribution, exhibits the strongest sensitivity to the nuclear equation of state. It is demonstrated that for very central collisions, b=1 fm, the squeeze-out is visible even in the double-differential cross section. This is experimentally accessible by studying azimuthally symmetric events, as confirmed recently by data of the European 4π detector collaboration at Gesellchaft für Schwerionforschung Darmstadt.
If density isomers exist they can be detected by measuring the excitation function of subthreshold kaon production. When the system reaches the density where the density isomer has influence on the equation of state (which depends on the beam energy and on the optical potential), we observe a jump in the cross section of the kaons whereas other observables change little. Above threshold Λ¯’s or p¯’s may be used to continue the search. This is the result of microscopic Boltzman-Uehling-Uhlenbeck calculations.
The article connects two strands of the recent sociolegal debate: (1) the empirical discovery of new forms of spontaneous law in die Course of globalization, and (2) the emergence of deconstructive theories of law that undermine the law's hierarchy. The article puts forward the thesis that law's hierarchy has successfully resisted all old and new attempts at its deconstruction; it breaks, however, under the pressures of globalization that produced a global law without the state, as self-created law of global society that has no institutionalized support whatsoever in international poliucs and public international law. Consequently, the article criticizes deconstructive theories for their lack of autological analysis. These theories do not take into account the historical condicions of deconstruction. Accordingly, deconstructive analysis of law would have to look for new legal distinctions that are plausible under the new condicions of a doubly fragmented global society. The article sketches the contours of an emerging polycontextural law.
Jura Studieren
(1968)
The illusion of apparent motion can be induced when visual stimuli are successively presented at different locations. It has been shown in previous studies that motion-sensitive regions in extrastriate cortex are relevant for the processing of apparent motion, but it is unclear whether primary visual cortex (V1) is also involved in the representation of the illusory motion path. We investigated, in human subjects, apparent-motion-related activity in patches of V1 representing locations along the path of illusory stimulus motion using functional magnetic resonance imaging. Here we show that apparent motion caused a blood-oxygenation-level-dependent response along the V1 representations of the apparent-motion path, including regions that were not directly activated by the apparent-motion-inducing stimuli. This response was unaltered when participants had to perform an attention-demanding task that diverted their attention away from the stimulus. With a bistable motion quartet, we confirmed that the activity was related to the conscious perception of movement. Our data suggest that V1 is part of the network that represents the illusory path of apparent motion. The activation in V1 can be explained either by lateral interactions within V1 or by feedback mechanisms from higher visual areas, especially the motion-sensitive human MT/V5 complex.
We present a biologically-inspired system for real-time, feed-forward object recognition in cluttered scenes. Our system utilizes a vocabulary of very sparse features that are shared between and within different object models. To detect objects in a novel scene, these features are located in the image, and each detected feature votes for all objects that are consistent with its presence. Due to the sharing of features between object models our approach is more scalable to large object databases than traditional methods. To demonstrate the utility of this approach, we train our system to recognize any of 50 objects in everyday cluttered scenes with substantial occlusion. Without further optimization we also demonstrate near-perfect recognition on a standard 3-D recognition problem. Our system has an interpretation as a sparsely connected feed-forward neural network, making it a viable model for fast, feed-forward object recognition in the primate visual system.
In November 2005, a survey was begun of the wells in and around Hagia Sophia Church in Istanbul. The long-term goal of the survey is the understanding of the function of the tunnels and the water systems used for Hagia Sophia and its surroundings during the Byzantine and the Ottoman periods. Alternate research methods, such as geophysical research, will be used in future surveys. The 2005 survey examined the channels that run from under the narthex and continue northwards and the southwards of the building as well as channels that run towards the atrium, hippodrome, and garden in the north. The survey resulted in the first photos of the well-bottoms in the history of Hagia Sophia.
Gene trapping is a method of generating murine embryonic stem (ES) cell lines containing insertional mutations in known and novel genes. A number of international groups have used this approach to create sizeable public cell line repositories available to the scientific community for the generation of mutant mouse strains. The major gene trapping groups worldwide have recently joined together to centralize access to all publicly available gene trap lines by developing a user-oriented Website for the International Gene Trap Consortium (IGTC). This collaboration provides an impressive public informatics resource comprising ~45 000 well-characterized ES cell lines which currently represent ~40% of known mouse genes, all freely available for the creation of knockout mice on a non-collaborative basis. To standardize annotation and provide high confidence data for gene trap lines, a rigorous identification and annotation pipeline has been developed combining genomic localization and transcript alignment of gene trap sequence tags to identify trapped loci. This information is stored in a new bioinformatics database accessible through the IGTC Website interface. The IGTC Website (www.genetrap.org) allows users to browse and search the database for trapped genes, BLAST sequences against gene trap sequence tags, and view trapped genes within biological pathways. In addition, IGTC data have been integrated into major genome browsers and bioinformatics sites to provide users with outside portals for viewing this data. The development of the IGTC Website marks a major advance by providing the research community with the data and tools necessary to effectively use public gene trap resources for the large-scale characterization of mammalian gene function.
Kongressbericht: Auf der Tagung der Deutschen Gesellschaft für Allgemeinmedizin und Familienmedizin e.V. (DEGAM) 2004 entstand die Idee, E-Learning-Aktivitäten in der Allgemeinmedizin sichtbar zu machen und zu bündeln. Ein Kongress sollte die allgemeinmedizinischen Vertreter aus Lehre und Forschung sowie Industrievertreter zusammenbringen, um das Spektrum der Möglichkeiten und laufende Projekte kennen zu lernen. Mit motivierten Referenten, über 60 aktiven Teilnehmern und einem positiven Feedback, kann der Kongress in Frankfurt am 8. und 9. Juli 2005 als erster dieser Art in Deutschland als erfolgreich bezeichnet werden.
Background: Depression is a disorder with high prevalence in primary health care and a significant burden of illness. The delivery of health care for depression, as well as other chronic illnesses, has been criticized for several reasons and new strategies to address the needs of these illnesses have been advocated. Case management is a patient-centered approach which has shown efficacy in the treatment of depression in highly organized Health Maintenance Organization (HMO) settings and which might also be effective in other, less structured settings. Methods/Design: PRoMPT (PRimary care Monitoring for depressive Patients Trial) is a cluster randomised controlled trial with General Practice (GP) as the unit of randomisation. The aim of the study is to evaluate a GP applied case-management for patients with major depressive disorder. 70 GPs were randomised either to intervention group or to control group with the control group delivering usual care. Each GP will include 10 patients suffering from major depressive disorder according to the DSM-IV criteria. The intervention group will receive treatment based on standardized guidelines and monthly telephone monitoring from a trained practice nurse. The nurse investigates the patient's status concerning the MDD criteria, his adherence to GPs prescriptions, possible side effects of medication, and treatment goal attainment. The control group receives usual care – including recommended guidelines. Main outcome measure is the cumulative score of the section depressive disorders (PHQ-9) from the German version of the Prime MD Patient Health Questionnaire (PHQ-D). Secondary outcome measures are the Beck-Depression-Inventory, self-reported adherence (adapted from Moriskey) and the SF-36. In addition, data are collected about patients' satisfaction (EUROPEP-tool), medication, health care utilization, comorbidity, suicide attempts and days out of work. The study comprises three assessment times: baseline (T0) , follow-up after 6 months (T1) and follow-up after 12 months (T2). Discussion: Depression is now recognized as a disorder with a high prevalence in primary care but with insufficient treatment response. Case management seems to be a promising intervention which has the potential to bridge the gap of the usually time-limited and fragmented provision of care. Case management has been proven to be effective in several studies but its application in the private general medical practice setting remains unclear.
Background: Diabetes model projects in different regions of Germany including interventions such as quality circles, patient education and documentation of medical findings have shown improvements of HbA1c levels, blood pressure and occurrence of hypoglycaemia in before-after studies (without control group). In 2002 the German Ministry of Health defined legal regulations for the introduction of nationwide disease management programs (DMP) to improve the quality of care in chronically ill patients. In April 2003 the first DMP for patients with type 2 diabetes was accredited. The evaluation of the DMP is essential and has been made obligatory in Germany by the Fifth Book of Social Code. The aim of the study is to assess the effectiveness of DMP by example of type 2 diabetes in the primary care setting of two German federal states (Rheinland-Pfalz and Sachsen-Anhalt). Methods/Design: The study is three-armed: a prospective cluster-randomized comparison of two interventions (DMP 1 and DMP 2) against routine care without DMP as control group. In the DMP group 1 the patients are treated according to the current situation within the German-Diabetes-DMP. The DMP group 2 represents diabetic care within ideally implemented DMP providing additional interventions (e.g. quality circles, outreach visits). According to a sample size calculation a sample size of 200 GPs (each GP including 20 patients) will be required for the comparison of DMP 1 and DMP 2 considering possible drop-outs. For the comparison with routine care 4000 patients identified by diabetic tracer medication and age (> 50 years) will be analyzed. Discussion: This study will evaluate the effectiveness of the German Diabetes-DMP compared to a Diabetes-DMP providing additional interventions and routine care in the primary care setting of two different German federal states.
Das Projekt LaMedica (http://www.lamedica.de) hat zum Ziel, eine multimediale Lehr- und Lernplattform zu entwickeln, Inhalte für die Medizin zu erstellen und diese in die Lehre zu implementieren. Es wurde eine on-line Autorenumgebung geschaffen, die sehr unterschiedliche didaktische Ansätze unterstützt: systematische und vernetzte Wissensvermittlung, fallbasiertes Lernen, Erstellung von Vorlesungen und Lernerfolgskontrolle. Die Lehrinhalte können zielgruppenspezifisch aufbereitet und dargestellt werden und richten sich insbesondere an Studenten, Ärzte in der Weiterbildung und Fachärzte. Eine on-line Medien-Datenbank unterstützt die Wiederverwendung und den Austausch von Inhalten auf der Basis eines Content-Management-Systems durch Verwendung des Learning Objects Metadata Standards (LOM). Die Förderung erfolgt durch das BMBF (FKZ NM054A).
Aims: This paper is a review of the literature on problem-related drinking of alcohol among medical doctors, and it deals with the epidemiology and results. Methods: A search of computer literature databases - PubMed and ETOH - was performed to locate articles reporting problem-related drinking among doctors, using population-based samples of doctors within the last two decades. Results: In the light of different definitions of problem-related drinking, there was found a breadth of prevalence of problem-related drinking - from heavy drinking and hazardous drinking (12%-16%) to misuse and dependence (6%-8%) - within the population-based samples of doctors. An increased risk was positively related to male doctors and doctors of the age of 40-45 years and older, and to some factors of work, lifestyle and health. Conclusion: For the future, it seems necessary to sensitise the research for problem-related drinking of doctors in Germany, e.g. initiating a representative survey, analysing the drinking of alcohol in the context of health, life-style and work-related factors.
Celiac disease
(2006)
Celiac disease is a chronic intestinal disease caused by intolerance to gluten. It is characterized by immune-mediated enteropathy, associated with maldigestion and malabsorption of most nutrients and vitamins. In predisposed individuals, the ingestion of gluten-containing food such as wheat and rye induces a flat jejunal mucosa with infiltration of lymphocytes. The main symptoms are: stomach pain, gas, and bloating, diarrhea, weight loss, anemia, edema, bone or joint pain. Prevalence for clinically overt celiac disease varies from 1:270 in Finland to 1:5000 in North America. Since celiac disease can be asymptomatic, most subjects are not diagnosed or they can present with atypical symptoms. Furthermore, severe inflammation of the small bowel can be present without any gastrointestinal symptoms. The diagnosis should be made early since celiac disease causes growth retardation in untreated children and atypical symptoms like infertility or neurological symptoms. Diagnosis requires endoscopy with jejunal biopsy. In addition, tissue-transglutaminase antibodies are important to confirm the diagnosis since there are other diseases which can mimic celiac disease. The exact cause of celiac disease is unknown but is thought to be primarily immune mediated (tissue-transglutaminase autoantigen); often the disease is inherited. Management consists in life long withdrawal of dietary gluten, which leads to significant clinical and histological improvement. However, complete normalization of histology can take years.
Prostaglandin E2 (PGE2) plays an important role in bone development and metabolism. To interfere therapeutically in the PGE2 pathway, however, knowledge about the involved enzymes (cyclooxygenases) and receptors (PGE2 receptors) is essential. We therefore examined the production of PGE2 in cultured growth plate chondrocytes in vitro and the effects of exogenously added PGE2 on cell proliferation. Furthermore, we analysed the expression and spatial distribution of cyclooxygenase (COX)-1 and COX-2 and PGE2 receptor types EP1, EP2, EP3 and EP4 in the growth plate in situ and in vitro. PGE2 synthesis was determined by mass spectrometry, cell proliferation by DNA [3H]-thymidine incorporation, mRNA expression of cyclooxygenases and EP receptors by RT-PCR on cultured cells and in homogenized growth plates. To determine cellular expression, frozen sections of rat tibial growth plate and primary chondrocyte cultures were stained using immunohistochemistry with polyclonal antibodies directed towards COX-1, COX-2, EP1, EP2, EP3, and EP4. Cultured growth plate chondrocytes transiently secreted PGE2 into the culture medium. Although both enzymes were expressed in chondrocytes in vitro and in vivo, it appears that mainly COX-2 contributed to PGE2-dependent proliferation. Exogenously added PGE2 stimulated DNA synthesis in a dose-dependent fashion and gave a bell-shaped curve with a maximum at 10-8 M. The EP1/EP3 specific agonist sulprostone and the EP1-selective agonist ONO-D1-004 increased DNA synthesis. The effect of PGE2 was suppressed by ONO-8711. The expression of EP1, EP2, EP3, and EP4 receptors in situ and in vitro was observed; EP2 was homogenously expressed in all zones of the growth plate in situ, whereas EP1 expression was inhomogenous, with spared cells in the reserve zone. In cultured cells these four receptors were expressed in a subset of cells only. The most intense staining for the EP1 receptor was found in polygonal cells surrounded by matrix. Expression of receptor protein for EP3 and EP4 was observed also in rat growth plates. In cultured chrondrocytes, however, only weak expression of EP3 and EP4 receptor was detected. We suggest that in growth plate chondrocytes, COX-2 is responsible for PGE2 release, which stimulates cell proliferation via the EP1 receptor.
Herman P. Schwan [1915–2005] was a distinguished scientist and engineer, and a founding father of the field of biomedical engineering. A man of integrity, Schwan influenced the lives of many, including his wife and children, and his many students and colleagues. Active in science until nearly the end of his life, he will be very much missed by his family and many colleagues.
High-throughput gene trapping is a random approach for inducing insertional mutations across the mouse genome. This approach uses gene trap vectors that simultaneously inactivate and report the expression of the trapped gene at the insertion site, and provide a DNA tag for the rapid identification of the disrupted gene. Gene trapping has been used by both public and private institutions to produce libraries of embryonic stem (ES) cells harboring mutations in single genes. Presently,~ 66% of the protein coding genes in the mouse genome have been disrupted by gene trap insertions. Among these, however, genes encoding signal peptides or transmembrane domains (secretory genes) are underrepresented because they are not susceptible to conventional trapping methods. Here, we describe a high-throughput gene trapping strategy that effectively targets secretory genes. We used this strategy to assemble a library of ES cells harboring mutations in 716 unique secretory genes, of which 61% were not trapped by conventional trapping, indicating that the two strategies are complementary. The trapped ES cell lines, which can be ordered from the International Gene Trap Consortium (http://www.genetrap.org), are freely available to the scientific community.