Search

Energy and biomass production in cancer cells are largely supported by aerobic glycolysis in what is called the Warburg effect. The process is regulated by key enzymes, among which phosphofructokinase PFK-2 plays a significant role by producing fructose-2,6-biphosphate; the most potent activator of the glycolysis rate-limiting step performed by phosphofructokinase PFK-1. Herein, the synthesis, biological evaluation and structure-activity relationship of novel inhibitors of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), which is the ubiquitous and hypoxia-induced isoform of PFK-2, are reported. X-ray crystallography and docking were instrumental in the design and optimisation of a series of N-aryl 6-aminoquinoxalines. The most potent representative, N-(4-methanesulfonylpyridin-3-yl)-8-(3-methyl-1-benzothiophen-5-yl)quinoxalin-6-amine, displayed an IC50 of 14 nm for the target and an IC50 of 0.49 μm for fructose-2,6-biphosphate production in human colon carcinoma HCT116 cells. This work provides a new entry in the field of PFKFB3 inhibitors with potential for development in oncology.

We investigate the formation of a galaxy reaching a virial mass of $~ 10^8$ solar mass at $z=10$ by carrying out a zoomed radiation-hydrodynamical cosmological simulation. This simulation traces Population~III (Pop~III) star formation, characterized by a modestly top-heavy initial mass function (IMF), and considers stellar feedback such as photoionization heating from Pop III and Population~II (Pop~II) stars, mechanical and chemical feedback from supernovae (SNe), and X-ray feedback from accreting black holes (BHs) and high-mass X-ray binaries (HMXBs). We self-consistently impose a transition in star formation mode from top-heavy Pop III to low-mass Pop~II, and find that the star formation rate in the computational box is dominated by Pop~III until $z=13$, and by Pop~II thereafter. The simulated galaxy experiences bursty star formation, with a substantially reduced gas content due to photoionization heating from Pop~III and Pop~II stars, together with SN feedback. All the gas within the simulated galaxy is metal-enriched above $10^{-5}$ solar, such that there are no remaining pockets of primordial gas. The simulated galaxy has an estimated observed flux of $~10^{-3} nJy$, which is too low to be detected by the James Webb Space Telescope (JWST) without strong lensing amplification. We also show that our simulated galaxy is similar in terms of stellar mass to Segue 2, the least luminous dwarf known in the Local Group., Comment: 18 pages 14 figures, Accepted for publication in MNRAS

If intelligent algorithms are the rockets of self-driving cars, then the data that is used to train and validate these algorithms can be considered the fuel on which these cars are running. Indeed, developing algorithms for self-driving cars requires many iterations on large sets of data which are collected under various real-case driving scenarios, and this is especially so as these algorithms increasingly incorporate deep neural nets.

Recent work suggests that the first generation of stars, the so-called Population III (Pop III), could have formed primarily in binaries or as members of small multiple systems. Here we investigate the impact of X-ray feedback from High-Mass X-ray Binaries (HMXBs) left behind in stellar binary systems after the primary forms a black hole (BH), accreting gas at a high rate from the companion, a process that is thought to be favored at the low metallicities characteristic of high-redshift gas. Thanks to their large mean free path, X-rays are capable of preionizing and preheating the gas in the intergalactic medium (IGM) and in haloes long before the reionization of the Universe is complete, and thus could have strongly affected the formation of subsequent generations of stars as well as reionization. We have carried out zoomed hydrodynamical cosmological simulations of minihaloes, accounting for the formation of Pop III stars and their collapse into BHs and HMXBs, and the associated radiation-hydrodynamic feedback from UV and X-ray photons. We find no strong net feedback from HMXBs on the simulated star formation history. On the other hand, the preheating of the IGM by HMXBs leads to a strong suppression of small-scale structures and significantly lowers the recombination rate in the IGM, thus yielding a net positive feedback on reionization. We further show that X-ray feedback from HMXBs can augment the ionizing feedback from the Pop III progenitor stars to suppress gas accretion onto the first BHs, limiting their growth into supermassive BHs. Finally, we show that X-ray ionization by HMXBs leaves distinct signatures in the properties of the high-redshift hydrogen that may be probed in upcoming observations of the redshifted 21cm spin-flip line., 20 pages, 12 figures. Accepted for publication in MNRAS

A substantial fraction of all ionizing photons originate from radiative recombinations. However, in radiative transfer calculations this recombination radiation is often assumed to be absorbed 'on-the-spot' because for most methods the computational cost associated with the inclusion of gas elements as sources is prohibitive. We present a new, CPU and memory efficient implementation for the transport of ionizing recombination radiation in the TRAPHIC radiative transfer scheme. TRAPHIC solves the radiative transfer equation by tracing photon packets at the speed of light and in a photon-conserving manner in spatially adaptive smoothed particle hydrodynamics simulations. Our new implementation uses existing features of the TRAPHIC scheme to add recombination radiation at no additional cost in the limit in which the fraction of the simulation box filled with radiation approaches 1. We test the implementation by simulating an HII region in photoionization equilibrium and comparing to reference solutions presented in the literature, finding excellent agreement. We apply our implementation to discuss the evolution of the HII region to equilibrium. We show that the widely used case A and B approximations yield accurate ionization profiles only near the source and near the ionization front, respectively. We also discuss the impact of recombination radiation on the geometry of shadows behind optically thick absorbers. We demonstrate that the shadow region may be completely ionized by the diffuse recombination radiation field and discuss the important role of heating by recombination radiation in the shadow region., Comment: 16 pages, 10 figures, accepted for publication in MNRAS

It is often assumed that local sources of ionizing radiation have little impact on the distribution of HI in the post-reionization Universe. While this is a good assumption for the IGM, analytic arguments suggest that local sources may typically be more important than the background radiation for high column density absorbers (N_HI > 10^17 /cm^2). We post-process cosmological simulations with accurate radiation transport to investigate the impact of local stellar sources on the HI distribution. We demonstrate that the limited numerical resolution and the simplified treatment of the ISM that are typical of current cosmological simulations provide significant challenges, but that many of the problems can be overcome by taking two steps. First, using ISM particles rather than stellar particles as sources results in a much better sampling of the source distribution. Second, by rescaling the source luminosities so that the amount of radiation escaping into the IGM agrees with that required to produce the observed background, many of the results become insensitive to errors in the predicted fraction of the radiation that escapes the immediate vicinity of the sources. By adopting this strategy and by varying the assumptions about the structure of the unresolved ISM, we conclude that we can robustly estimate the effect of local sources for column densities N_HI << 10^21 /cm^2. However, neither the escape fraction of ionizing radiation nor the effect of local sources on the abundance of N_HI >~ 10^21 systems can be predicted with confidence. We find that local stellar radiation is unimportant for N_HI << 10^17, but that it can affect Lyman Limit and DLA systems. For 10^18 < N_HI < 10^21 the impact of local sources increases with redshift. At z = 5 the abundance of absorbers with N_HI >> 10^17 is substantially reduced, but at z = 0 the reduction only becomes significant for N_HI >~ 10^21 /cm^2., 19 pages, 12 figures; Accepted for publication in MNRAS

We use a set of cosmological simulations combined with radiative transfer calculations to investigate the distribution of neutral hydrogen in the post-reionization Universe. We assess the contributions from the metagalactic ionizing background, collisional ionization and diffuse recombination radiation to the total ionization rate at redshifts z=0-5. We find that the densities above which hydrogen self-shielding becomes important are consistent with analytic calculations and previous work. However, because of diffuse recombination radiation, whose intensity peaks at the same density, the transition between highly ionized and self-shielded regions is smoother than what is usually assumed. We provide fitting functions to the simulated photoionization rate as a function of density and show that post-processing simulations with the fitted rates yields results that are in excellent agreement with the original radiative transfer calculations. The predicted neutral hydrogen column density distributions agree very well with the observations. In particular, the simulations reproduce the remarkable lack of evolution in the column density distribution of Lyman limit and weak damped Ly\alpha\ systems below z = 3. The evolution of the low column density end is affected by the increasing importance of collisional ionization with decreasing redshift. On the other hand, the simulations predict the abundance of strong damped Ly\alpha\ systems to broadly track the cosmic star formation rate density., Comment: 21 pages (including 6 pages for references and appendixes), 13 figures; Accepted for publication in MNRAS

The core of autonomous driving are intelligent algorithms that control real-time actions based on the recordings of on-board sensors which monitor the environment as well as the internal states of the car. Many open issues are to be solved before the vision of autonomously driving fleets of cars employing such algorithms will become reality. Amongst them is how to structure the process of developing the algorithms to meet functional and non-functional requirements.

We present an extension of TRAPHIC, the method for radiative transfer of ionising radiation in smoothed particle hydrodynamics simulations that we introduced in Pawlik & Schaye (2008). The new version keeps all advantages of the original implementation: photons are transported at the speed of light, in a photon-conserving manner, directly on the spatially adaptive, unstructured grid traced out by the particles, in a computation time that is independent of the number of radiation sources, and in parallel on distributed memory machines. We extend the method to include multiple frequencies, both hydrogen and helium, and to model the coupled evolution of the temperature and ionisation balance. We test our methods by performing a set of simulations of increasing complexity and including a small cosmological reionisation run. The results are in excellent agreement with exact solutions, where available, and also with results obtained with other codes if we make similar assumptions and account for differences in the atomic rates used. We use the new implementation to illustrate the differences between simulations that compute photoheating in the grey approximation and those that use multiple frequency bins. We show that close to ionising sources the grey approximation asymptotes to the multi-frequency result if photoheating rates are computed in the optically thin limit, but that the grey approximation breaks down everywhere if, as is often done, the optically thick limit is assumed.

A new class of dyes, in which the self-assembling property of surfactants is combined with the capability for light energy propagation over long distances in dye J-aggregates, is described. This has been achieved by the syntheses of achiral 5,5′,6,6′-tetrachlorobenzimidacarbocyanine dyes 1, possessing systematically varied hydrophobic and hydrophilic substituents at their nitrogen atoms. These substituents are introduced into the 5,6-dichlorobenzimidazole precursor 3 by substitution, either firstly by nucleophilic reaction with ψ-bromoalkylnitriles and secondly by quaternization with alkyl bromides (route II) or firstly by nucleophilic reaction with alkyl bromides and secondly by quaternization with ψ-bromoalkylnitriles or ψ-bromoalkyl esters (route III) and subsequent saponification. The UV/Vis spectra of 20 differently substituted dyes containing the same chromophore 1 have been investigated. The spectra of the dye monomers in dimethyl sulfoxide are nearly identical, with no signs of optically activity, whereas in aqueous alkaline solutions quite different spectra are obtained for the dyes, indicating the formation of different aggregates depending on the nitrogen substituents. One of these types of J-aggregate is optically inactive and displays a single red-shifted (with respect to the dye monomers) absorption band, resembling the behaviour of J-aggregates of common cyanine dyes. In the cases of strongly amphiphilic 5,5′,6,6′-benzimidacarbocyanines 1 with 1,1′-dialkyl substituents longer than hexyl and 3,3′-bis(2-carboxyethyl), 3,3′-bis(3-carboxypropyl) or 3,3′-bis(3-sulfopropyl) substituents, a new type of J-aggregate is formed, and is distinguished by a doubly or even triply split J-absorption band that displays optical activity. A third type of aggregate showing different spectral behaviour occurs when the dyes contain very short 3,3′-bis(carboxymethyl) substituents or strongly hydrophobic fluorinated octyl groups, or when all four nitrogen atoms are identically substituted by hydrophilic 3-carboxypropyl groups. The various types of dye aggregates have been characterized through UV/Vis spectroscopic parameters such as the positions and widths of the absorption and fluorescence bands, the Stokes′ shifts, the coupling constants, and the strength of the J-band splitting. The results provide new prospects for the development of new artificial light-harvesting systems as well as for the understanding of the evolution of asymmetry in the biosphere. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

We present a suite of cosmological radiation-hydrodynamical simulations of the assembly of galaxies driving the reionization of the intergalactic medium (IGM) at z >~ 6. The simulations account for the hydrodynamical feedback from photoionization heating and the explosion of massive stars as supernovae (SNe). Our reference simulation, which was carried out in a box of size 25 comoving Mpc/h using 2 x 512^3 particles, produces a reasonable reionization history and matches the observed UV luminosity function of galaxies. Simulations with different box sizes and resolutions are used to investigate numerical convergence, and simulations in which either SNe or photoionization heating or both are turned off, are used to investigate the role of feedback from star formation. Ionizing radiation is treated using accurate radiative transfer at the high spatially adaptive resolution at which the hydrodynamics is carried out. SN feedback strongly reduces the star formation rates (SFRs) over nearly the full mass range of simulated galaxies and is required to yield SFRs in agreement with observations. Photoheating helps to suppress star formation in low-mass galaxies, but its impact on the cosmic SFR is small. Because the effect of photoheating is masked by the strong SN feedback, it does not imprint a signature on the UV galaxy luminosity function, although we note that our resolution is insufficient to model star-forming minihaloes cooling through molecular hydrogen transitions. Photoheating does provide a strong positive feedback on reionization because it smooths density fluctuations in the IGM, which lowers the IGM recombination rate substantially. Our simulations demonstrate a tight non-linear coupling of galaxy formation and reionization, motivating the need for the accurate and simultaneous inclusion of photoheating and SN feedback in models of the early Universe., 22 pages, 10 figures. Accepted for publication in MNRAS. Minor changes to match the accepted version, including an updated comparison of the simulated reionization optical depth with the latest observational estimate (figure 2)

We use cosmological simulations to assess how the explosion of the first stars in supernovae (SNe) influences early cosmic history. Specifically, we investigate the impact by SNe on the host systems for Population~III (Pop~III) star formation and explore its dependence on halo environment and Pop~III progenitor mass. We then trace the evolution of the enriched gas until conditions are met to trigger second-generation star formation. To this extent, we quantify the recovery timescale, which measures the time delay between a Pop~III SN explosion and the appearance of cold, dense gas, out of which second-generation stars can form. We find that this timescale is highly sensitive to the Pop~III progenitor mass, and less so to the halo environment. For more massive progenitors, including those exploding in pair instability SNe, second-generation star formation is delayed significantly, for up to a Hubble time. The dependence of the recovery time on the mass of the SN progenitor is mainly due to the ionizing impact of the progenitor star. Photoionization heating increases the gas pressure and initiates a hydrodynamical response that reduces the central gas density, an effect that is stronger in more massive. The gas around lower mass Pop~III stars remains denser and hence the SN remnants cool more rapidly, facilitating the subsequent re-condensation of the gas and formation of a second generation of stars. In most cases, the second-generation stars are already metal-enriched to ~2-5 X 10^{-4}\zsun, thus belonging to Population~II. The recovery timescale is a key quantity governing the nature of the first galaxies, able to host low-mass, long-lived stellar systems. These in turn are the target of future deep-field campaigns with the James Webb Space Telescope., 12 pages, 10 figures, Accepted for publication in MNRAS

PURPOSE: To examine if RARE urography may replace conventional intravenous urography in patients with suspected urinary obstruction in pelvic tumours. MATERIALS AND METHODS: In a prospective trial on 120 patients with pelvic tumours scheduled for operation, biplanar RARE urography was performed and compared to conventional intravenous urography and ultrasound findings. RESULTS: In 30 out of 120 patients an ureteric obstruction was diagnosed by ultrasound. Sensitivity of RARE urography for obstruction was 98% as compared to 60% in conventional intravenous urography. In 12 patients additional retrograde cystoureterography showed a sensitivity of 83%. Specificity of RARE urography and intravenous urography was 100%. In combination with axial MR tomography RARE urography yielded a more precise localisation of the site of obstruction and the underlying cause (98%) as compared to conventional urography (60%) and ultrasound (56%). CONCLUSION: By use of RARE urography urinary obstruction can be reliably demonstrated or ruled out. Combining RARE urography with tomographic MR imaging allows the precise depiction of the site of the obstruction and may demonstrate the underlying pathology.

We use cosmological simulations of high-redshift minihalos to investigate the effect of dark matter annihilation (DMA) on the collapse of primordial gas. We numerically investigate the evolution of the gas as it assembles in a Population III stellar disk. We find that when DMA effects are neglected, the disk undergoes multiple fragmentation events beginning at ~ 500 yr after the appearance of the first protostar. On the other hand, DMA heating and ionization of the gas speeds the initial collapse of gas to protostellar densities and also affects the stability of the developing disk against fragmentation, depending on the DM distribution. We compare the evolution when we model the DM density with an analytical DM profile which remains centrally peaked, and when we simulate the DM profile using N-body particles (the 'live' DM halo). When utilizing the analytical DM profile, DMA suppresses disk fragmentation for ~ 3500 yr after the first protostar forms, in agreement with earlier work. However, when using a 'live' DM halo, the central DM density peak is gradually flattened due to the mutual interaction between the DM and the rotating gaseous disk, reducing the effects of DMA on the gas, and enabling secondary protostars of mass ~ 1 M_sol to be formed within ~ 900 yr. These simulations demonstrate that DMA is ineffective in suppressing gas collapse and subsequent fragmentation, rendering the formation of long-lived dark stars unlikely. However, DMA effects may still be significant in the early collapse and disk formation phase of primordial gas evolution., 17 pages, 11 figures, to appear in MNRAS

We present measurements of the specific ultraviolet luminosity density from a sample of 483 galaxies at 650%. Combining our observations with constraints on the emission rate of ionizing photons from Ly-alpha forest observations at z=6, we can constrain f_esc7, consistent with a number of complementary reionization probes. If faint galaxies dominate reionization, future JWST observations will probe deep enough to see them, providing an indirect constraint on the ionizing photon escape fraction [abridged]., Comment: 16 pages, 7 figures, Submitted to the Astrophysical Journal

We investigate how radiative feedback from the first stars affects the assembly of the first dwarf galaxies. We perform cosmological zoomed smoothed particle hydrodynamics simulations of a galaxy assembling inside a halo reaching a virial mass ∼ 109 M⊙ at z = 10. The simulations follow the non-equilibrium chemistry and cooling of primordial gas and the subsequent conversion of the cool dense gas into massive metal-free stars. To quantify the radiative feedback, we compare a simulation in which stars emit both molecular hydrogen dissociating and hydrogen ionizing radiation with a simulation in which stars do not emit radiation but remain dark. Photodissociation and photoionization exert a strong negative feedback on the assembly of the galaxy inside the minihalo progenitor, impeding gas condensation and suppressing star formation. The radiative feedback on the gas implies a suppression of the central dark matter densities in the minihalo by factors of up to a few, which is a significant deviation from the singular isothermal density profile characterizing the dark matter distribution in the absence of radiative feedback. The properties of the galaxy become insensitive to the inclusion of radiation once the minihalo turns into an atomic cooler. The formation of a rotationally supported extended disk inside the atomically cooling galaxy therefore is a robust outcome of our simulations. Our simulations make predictions for observations with the upcoming James Webb Space Telescope.

We investigate how radiative feedback from the first stars affects the assembly of the first dwarf galaxies. We perform cosmological zoomed SPH simulations of a dwarf galaxy assembling inside a halo of virial mass 10^9 solar at z = 10. The simulations follow the non-equilibrium chemistry/cooling of primordial gas and the conversion of the gas into metal-free stars. To quantify the radiative feedback, we compare a simulation in which stars emit both molecular hydrogen dissociating and hydrogen/helium ionizing radiation with a simulation in which stars emit only dissociating radiation, and with a simulation in which stars remain dark. Photodissociation and -ionization exert a strong negative feedback on the assembly of the simulated galaxy. Gas condensation is strongly impeded, and star formation is strongly suppressed in comparison with the simulation in which stars remain dark. The feedback on the gas implies a suppression of the central dark matter densities in the minihalo progenitor by factors of up to a few, which is a significant deviation from the singular isothermal density profile characterizing the dark matter distribution in the absence of radiative feedback. The evolution of gas densities, star formation rates, and the distribution of dark matter becomes insensitive to the inclusion of dissociating radiation in the late stages of the minihalo assembly, and it becomes insensitive to the inclusion of ionizing radiation once the minihalo turns into an atomically cooling galaxy. The formation of an extended disk inside the dwarf galaxy is a robust outcome not affected by the inclusion of radiation. We estimate that dwarf galaxies such as simulated here will be among the faintest galaxies the upcoming James Webb Space Telescope will detect. Our conclusions are subject to our neglect of feedback from supernovae and chemical enrichment as well as to cosmic variance. [abridged], Comment: 25 pages (including 5 pages appendix), 13 figures. Accepted for publication in ApJ

We numerically study the mutual interaction between dark matter (DM) and Population III (Pop III) stellar systems in order to explore the possibility of Pop III dark stars within this physical scenario. We perform a cosmological simulation, initialized at z ~ 100, which follows the evolution of gas and DM. We analyze the formation of the first minihalo at z ~ 20 and the subsequent collapse of the gas to densities of 10^12 cm^-3. We then use this simulation to initialize a set of smaller-scale `cut-out' simulations in which we further refine the DM to have spatial resolution similar to that of the gas. We test multiple DM density profiles, and we employ the sink particle method to represent the accreting star-forming region. We find that, for a range of DM configurations, the motion of the Pop III star-disk system serves to separate the positions of the protostars with respect to the DM density peak, such that there is insufficient DM to influence the formation and evolution of the protostars for more than ~ 5000 years. In addition, the star-disk system causes gravitational scattering of the central DM to lower densities, further decreasing the influence of DM over time. Any DM-powered phase of Pop III stars will thus be very short-lived for the typical multiple system, and DM will not serve to significantly prolong the life of Pop III stars.

We study how the first galaxies were assembled under feedback from the accretion onto a central black hole (BH) that is left behind by the first generation of metal-free stars through selfconsistent, cosmological simulations. X-ray radiation fromthe accretion of gas onto BH remnants of Population III (Pop III) stars, or from high-mass X-ray binaries (HMXBs), again involving Pop III stars, influences the mode of second generation star formation. We track the evolution of the black hole accretion rate and the associated X-ray feedback startingwith the death of the Pop III progenitor star inside a minihalo and following the subsequent evolution of the black hole as the minihalo grows to become an atomically cooling galaxy. We find that X-ray photoionization heating from a stellar-mass BH is able to quench further star formation in the host halo at all times before the halo enters the atomic cooling phase. X-ray radiation from a HMXB, assuming a luminosity close to the Eddington value, exerts an even stronger...

Theoretical models predict that some of the first stars ended their lives as extremely energetic Pair Instability Supernovae (PISNe). With energies approaching 1053 erg, these supernovae are expected to be within the detection limits of the upcoming James Webb Space Telescope (JWST) allowing observational constraints to be placed on the properties of the first stars. We estimate the source density of PISNe using a semi-analytic Press-Schecter based approach informed by cosmological simulations, with an upper limit of ∼0.2 PISNe visible per JWST field of view at any given time. We find that the main obstacle to observing PISNe is their scarcity rather than their faintness. Given this we suggest a mosaic style search strategy for detecting PISNe from the first stars.

The James Webb Space Telescope (JWST) will enable observations of galaxies at redshifts z > 10 and hence allow to test our current understanding of structure formation at very early times. Previous work has shown that the very first galaxies inside halos with virial temperatures T < 10^4 K and masses M < 10^8 M_sun at z > 10 are probably too faint, by at least one order of magnitude, to be detected even in deep exposures with JWST. The light collected with JWST may therefore be dominated by radiation from galaxies inside ten times more massive halos. We use cosmological zoomed smoothed particle hydrodynamics simulations to investigate the assembly of such galaxies and assess their observability with JWST. We compare two simulations that are identical except for the inclusion of non-equilibrium H/D chemistry and radiative cooling by molecular hydrogen. In both simulations a large fraction of the halo gas settles in two nested, extended gas disks which surround a compact massive gas core. The presence of molecular hydrogen allows the disk gas to reach low temperatures and to develop marked spiral structure but does not qualitatively change its stability against fragmentation. We post-process the simulated galaxies by combining idealized models for star formation with stellar population synthesis models to estimate the luminosities in nebular recombination lines as well as in the ultraviolet continuum. We demonstrate that JWST will be able to constrain the nature of the stellar populations in galaxies such as simulated here based on the detection of the He1640 recombination line. Extrapolation of our results to halos with masses both lower and higher than those simulated shows that JWST may find up to a thousand star-bursting galaxies in future deep exposures of the z > 10 universe., 19 pages, 13 figures. Accepted for publication in ApJ. Revised version with improved presentations and discussions

One of the aims of the Low Frequency Array (LOFAR) Epoch of Reionization (EoR) project is to measure the power spectrum of variations in the intensity of redshifted 21-cm radiation from the EoR. The sensitivity with which this power spectrum can be estimated depends on the level of thermal noise and sample variance, and also on the systematic errors arising from the extraction process, in particular from the subtraction of foreground contamination. We model the extraction process using realistic simulations of the cosmological signal, the foregrounds and noise, and so estimate the sensitivity of the LOFAR EoR experiment to the redshifted 21-cm power spectrum. Detection of emission from the EoR should be possible within 360 hours of observation with a single station beam. Integrating for longer, and synthesizing multiple station beams within the primary (tile) beam, then enables us to extract progressively more accurate estimates of the power at a greater range of scales and redshifts. We discuss different observational strategies which compromise between depth of observation, sky coverage and frequency coverage. A plan in which lower frequencies receive a larger fraction of the time appears to be promising. We also study the nature of the bias which foreground fitting errors induce on the inferred power spectrum, and discuss how to reduce and correct for this bias. The angular and line-of-sight power spectra have different merits in this respect, and we suggest considering them separately in the analysis of LOFAR data.

Detecting redshifted 21cm emission from neutral hydrogen in the early Universe promises to give direct constraints on the epoch of reionization (EoR). It will, though, be very challenging to extract the cosmological signal (CS) from foregrounds and noise which are orders of magnitude larger. Fortunately, the signal has some characteristics which differentiate it from the foregrounds and noise, and we suggest that using the correct statistics may tease out signatures of reionization. We generate mock datacubes simulating the output of the Low Frequency Array (LOFAR) EoR experiment. These cubes combine realistic models for Galactic and extragalactic foregrounds and the noise with three different simulations of the CS. We fit out the foregrounds, which are smooth in the frequency direction, to produce residual images in each frequency band. We denoise these images and study the skewness of the one-point distribution in the images as a function of frequency. We find that, under sufficiently optimistic assumptions, we can recover the main features of the redshift evolution of the skewness in the 21cm signal. We argue that some of these features - such as a dip at the onset of reionization, followed by a rise towards its later stages - may be generic, and give us a promising route to a statistical detection of reionization., 11 pages, 10 figures. One figure added. Other small changes to match accepted version

We present TRAPHIC, a novel radiative transfer scheme for Smoothed Particle Hydrodynamics (SPH) simulations. TRAPHIC is designed for use in simulations exhibiting a wide dynamic range in physical length scales and containing a large number of light sources. It is adaptive both in space and in angle and can be employed for application on distributed memory machines. The commonly encountered computationally expensive scaling with the number of light sources in the simulation is avoided by introducing a source merging procedure. The (time-dependent) radiative transfer equation is solved by tracing individual photon packets in an explicitly photon-conserving manner directly on the unstructured grid traced out by the set of SPH particles. To accomplish directed transport of radiation despite the irregular spatial distribution of the SPH particles, photons are guided inside cones. We present and test a parallel numerical implementation of TRAPHIC in the SPH code GADGET-2, specified for the transport of mono-chromatic hydrogen-ionizing radiation. The results of the tests are in excellent agreement with both analytic solutions and results obtained with other state-of-the-art radiative transfer codes., Comment: 31 pages, 20 figures. Accepted for publication in MNRAS. Revised version includes many clarifications and a new time-dependent radiative transfer calculation (fig. 19)

Photo-heating associated with reionisation and kinetic feedback from core-collapse supernovae have previously been shown to suppress the high-redshift cosmic star formation rate. Here we investigate the interplay between photo-heating and supernova feedback using a set of cosmological, smoothed particle hydrodynamics simulations. We show that photo-heating and supernova feedback mutually amplify each other's ability to suppress the star formation rate. Our results demonstrate the importance of the simultaneous, non-independent inclusion of these two processes in models of galaxy formation to estimate the strength of the total negative feedback they exert. They may therefore be of particular relevance to semi-analytic models in which the effects of photo-heating and supernova feedback are implicitly assumed to act independently of each other., Comment: 6 pages, 3 figures. Accepted for publication in MNRAS. Minor textual changes. Revised version with improved motivation and discussion

We demonstrate that a multiple delayed feedback is a powerful tool to control coherence properties of autonomous self-sustained oscillators. We derive the equation for the phase dynamics in presence of noise and delay, and analyze it analytically. In Gaussian approximation a closed set of equations for the frequency and the diffusion constant is obtained. Solutions of these equations are in good agreement with direct numerical simulations.

Arthritis psoriatica has been known for over 160 years, however, not long ago it became a separate nosologic unit. In 1964 American Rheumatological Society introduced the name arthritis psoriatica, which is obligatory nowadays. It was thought in the beginning that the inflammation may coexist with psoriasis accidentally only, whereas epidemiological studies, clinical observations and serologic data excluded such a simple relation. Since the international diagnostic criteria were established and also the rheumatoid factor was discovered it has been clear there's a direct relation between arthritis psoriatica and dermatologic changes of a psoriasis type. Therefore it is a disease where rheumatology and dermatology meet with each other. The aim of our study was to collect the knowledge about the diagnosis of arthritis psoriatica.

To examine if RARE urography may replace conventional intravenous urography in patients with suspected urinary obstruction in pelvic tumours.In a prospective trial on 120 patients with pelvic tumours scheduled for operation, biplanar RARE urography was performed and compared to conventional intravenous urography and ultrasound findings.In 30 out of 120 patients an ureteric obstruction was diagnosed by ultrasound. Sensitivity of RARE urography for obstruction was 98% as compared to 60% in conventional intravenous urography. In 12 patients additional retrograde cystoureterography showed a sensitivity of 83%. Specificity of RARE urography and intravenous urography was 100%. In combination with axial MR tomography RARE urography yielded a more precise localisation of the site of obstruction and the underlying cause (98%) as compared to conventional urography (60%) and ultrasound (56%).By use of RARE urography urinary obstruction can be reliably demonstrated or ruled out. Combining RARE urography with tomographic MR imaging allows the precise depiction of the site of the obstruction and may demonstrate the underlying pathology.

Planimetric studies of peritoneal surface area were performed in 10 humans, 12 rabbits, and 15 rats. It was found that the total peritoneal surface area (TPSA) correlated in humans with body surface area (BSA) (r = 0.98, p0.0001) and body weight (r = 0.93, p0.001), and correlated in animals with body weight (r = 0.80, p0.005 in rabbits; and r = 0.88, p0.0001 in rats). The area of parietal peritoneum was 18.1 +/- 1.8% of TPSA in humans, 17.8 +/- 1.0% of TPSA in rabbits, and 22.6 +/- 2.1% of TPSA in rats (p0.001 vs humans and rabbits). Additionally, the area of peritoneum covering the individual organs (expressed as % of TPSA) was different in humans, rabbits, and rats: for example, the area of peritoneum covering the diaphragm was 6.4 +/- 1.5% of TPSA in humans, which was larger than in animals (3.0 +/- 0.3% in rats, p0.0001 vs humans and rabbits; and only 2.1 +/- 0.4% in rabbits, p0.0001 vs humans). Presented results show that interspecies variation in the topography of the peritoneum should be taken into account when the results from experimental studies done on animals are extrapolated to humans.

Theoretical models predict that some of the first stars ended their lives as extremely energetic pair-instability supernovae (PISNe). With energies approaching 10^53 ergs, these supernovae are expected to be within the detection limits of the upcoming James Webb Space telescope (JWST), allowing observational constraints to be placed on the properties of the first stars. We estimate the source density of PISNe using a semi-analytic halo mass function based approach, accounting for the effects of feedback from star formation on the PISN rates using cosmological simulations. We estimate an upper limit of ~0.2 PISNe per JWST field of view at any given time. Feedback can reduce this rate significantly, e.g., lowering it to as little as one PISN per 4000 JWST fields of view for the most pessimistic explosion models. We also find that the main obstacle to observing PISNe from the first stars is their scarcity, not their faintness; exposures longer than a few times 10^4s will do little to increase the number of PISNe found. Given this we suggest a mosaic style search strategy for detecting PISNe from the first stars. Even rather high redshift PISNe are unlikely to be missed by moderate exposures, and a large number of pointings will be required to ensure a detection., Accepted for publication in ApJ. Substantially extended following referee feedback; rates revised downwards

We study how the first galaxies were assembled under feedback from the accretion onto a central black hole (BH) that is left behind by the first generation of metal-free stars through self-consistent, cosmological simulations. X-ray radiation from the accretion of gas onto BH remnants of Population III (Pop III) stars, or from high-mass X-ray binaries (HMXBs), again involving Pop III stars, influences the mode of second generation star formation. We track the evolution of the black hole accretion rate and the associated X-ray feedback starting with the death of the Pop III progenitor star inside a minihalo and following the subsequent evolution of the black hole as the minihalo grows to become an atomically cooling galaxy. We find that X-ray photoionization heating from a stellar-mass BH is able to quench further star formation in the host halo at all times before the halo enters the atomic cooling phase. X-ray radiation from a HMXB, assuming a luminosity close to the Eddington value, exerts an even stronger, and more diverse, feedback on star formation. It photoheats the gas inside the host halo, but also promotes the formation of molecular hydrogen and cooling of gas in the intergalactic medium and in nearby minihalos, leading to a net increase in the number of stars formed at early times. Our simulations further show that the radiative feedback from the first BHs may strongly suppress early BH growth, thus constraining models for the formation of supermassive BHs., 18 pages, 14 figures, accepted for publication in ApJ

The authors evaluated 60 epidurographies performed in patients with suspected compressing lesions in the vertebral canal. It was demonstrated that epidurography may be a useful method for diagnosis of pathological conditions in the vertebral canal, particularly in its thoracolumbar part. In many cases this method is sufficient for establishing full diagnosis, not infrequently it should be applied as a supplementary procedure (e.g. for evaluating the structure of the vertebral canal or for accurate assessment of the size of the tumour situated in the canal) and in cases with high-grade stenosis of the canal it is the method of choice. Moreover, it was found that epidurography is a method of low invasiveness, not harmful and well tolerated by the patients.