Evolution of the X-ray Emission of Radio-Quiet Quasars

We report new Chandra observations of seven optically faint, z \sim 4 radio-quiet quasars. We have combined these new observations with previous Chandra observations of radio-quiet quasars to create a sample of 174 sources. These sources have 0.1 < z < 4.7, and 10^{44} ergs s^{-1} < nu L_{nu} (2500 \AA) < 10^{48} ergs s^{-1}. The X-ray detection fraction is 90%. We find that the X-ray loudness of radio-quiet quasars decreases with UV luminosity and increases with redshift. The model that is best supported by the data has a linear dependence of optical-to-X-ray ratio, alpha_{ox}, on cosmic time, and a quadratic dependence of alpha_{ox} on log L_{UV}, where alpha_{ox} becomes X-ray quiet more rapidly at higher log L_{UV}. We find no significant evidence for a relationship between the X-ray photon index, Gamma_X, and the UV luminosity, and we find marginally significant evidence that the X-ray continuum flattens with increasing z (2 sigma). The Gamma_X-z anti-correlation may be the result of X-ray spectral curvature, redshifting of a Compton reflection component into the observed Chandra band, and/or redshifting of a soft excess out of the observed Chandra band. Using the results for Gamma_X, we show that the alpha_{ox}-z relationship is unlikely to be a spurious result caused by redshifting of the observable X-ray spectral region. A correlation between alpha_{ox} and z implies evolution of the accretion process. We present a qualitative comparison of these new results with models for accretion disk emission.Comment: Accepted by ApJ, 48 pages, 10 figures, 5 table

Two-Stage Interpretation of Changes in TEER of Intestinal Epithelial Layers Protected by Adhering Bifidobacteria During E. coli Challenges

Mechanisms of gastrointestinal protection by probiotic bacteria against infection involve amongst others, modulation of intestinal epithelial barrier function. Trans-epithelial electrical resistance (TEER) is widely used to evaluate cellular barrier functions. Here, we developed a two-stage interpretative model of the time-dependence of the TEER of epithelial layers grown in a transwell during Escherichia coli challenges in the absence or presence of adhering bifidobacteria. E. coli adhesion in absence or presence of adhering bifidobacteria was enumerated using selective plating. After 4-8 h, E. coli challenges increased TEER to a maximum due to bacterial adhesion and increased expression of a tight-junction protein [zonula occludens-1 (ZO-1)], concurrent with a less dense layer structure, that is indicative of mild epithelial layer damage. Before the occurrence of a TEER-maximum, decreases in electrical conductance (i.e., the reciprocal TEER) did not relate with para-cellular dextran-permeability, but after occurrence of a TEER-maximum, dextran-permeability and conductance increased linearly, indicative of more severe epithelial layer damage. Within 24 h after the occurrence of a TEER maximum, TEER decreased to below the level of unchallenged epithelial layers demonstrating microscopically observable holes and apoptosis. Under probiotic protection by adhering bifidobacteria, TEER-maxima were delayed or decreased in magnitude due to later transition from mild to severe damage, but similar linear relations between conductance and dextran permeability were observed as in absence of adhering bifidobacteria. Based on the time-dependence of the TEER and the relation between conductance and dextran-permeability, it is proposed that bacterial adhesion to epithelial layers first causes mild damage, followed by more severe damage after the occurrence of a TEER-maximum. The mild damage caused by E. coli prior to the occurrence of TEER maxima was reversible upon antibiotic treatment, but the severe damage after occurrence of TEER maxima could not be reverted by antibiotic treatment. Thus, single-time TEER is interpretable in two ways, depending whether increasing to or decreasing from its maximum. Adhering bifidobacteria elongate the time-window available for antibiotic treatment to repair initial pathogen damage to intestinal epithelial layers.</p

Observational Constraints on the Dependence of Radio-Quiet Quasar X-ray Emission on Black Hole Mass and Accretion Rate

In this work we use a sample of 318 radio-quiet quasars (RQQ) to investigate the dependence of the ratio of optical/UV flux to X-ray flux, alpha_ox, and the X-ray photon index, Gamma_X, on black hole mass, UV luminosity relative to Eddington, and X-ray luminosity relative to Eddington. Our sample is drawn from the SDSS, with X-ray data from ROSAT and Chandra, and optical data mostly from the SDSS; 153 of these sources have estimates of Gamma_X from Chandra. We estimate M_BH using standard estimates derived from the Hbeta, Mg II, and C IV broad emission lines. Our sample spans a broad range in black hole mass (10^6 < M_BH / M_Sun < 10^10) and redshift (z < 4.8). We find that alpha_ox increases with increasing M_BH and L_UV / L_Edd, and decreases with increasing L_X / L_Edd. In addition, we confirm the correlation seen in previous studies between Gamma_X and M_BH and both L_UV / L_Edd and L_X / L_Edd; however, we also find evidence that the dependence of Gamma_X of these quantities is not monotonic, changing sign at M_BH ~ 3 x 10^8 M_Sun. We argue that the alpha_ox correlations imply that the fraction of bolometric luminosity emitted by the accretion disk, as compared to the corona, increases with increasing accretion rate relative to Eddington. In addition, we argue that the Gamma_X trends are caused by a dependence of X-ray spectral index on accretion rate. We discuss our results within the context of accretion models with comptonizing corona, and discuss the implications of the alpha_ox correlations for quasar feedback. To date, this is the largest study of the dependence of RQQ X-ray parameters on black hole mass and related quantities, and the first to attempt to correct for the large statistical uncertainty in the broad line mass estimates.Comment: Accepted by ApJ, 23 pages, 15 figures, emulateapj styl

Escherichia coli Colonization of Intestinal Epithelial Layers In Vitro in the Presence of Encapsulated Bifidobacterium breve for Its Protection against Gastrointestinal Fluids and Antibiotics

Encapsulation of probiotic bacteria can enhance their functionality when used in combination with antibiotics for treating intestinal tract infections. The interaction strength of encapsulating shells, however, varies among the encapsulation methods and impacts encapsulation. Here, we compared the protection offered by encapsulating shells with different interaction strengths toward probiotic Bifidobacterium breve against simulated gastric fluid and tetracycline, including protamine-assisted SiO2 nanoparticle yolk-shell packing (weak interaction across a void), alginate gelation (intermediate interaction due to hydrogen binding), and ZIF-8 mineralization (strong interaction due to coordinate covalent binding). The presence of encapsulating shells was demonstrated using X-ray-photoelectron spectroscopy, particulate microelectrophoresis, and dynamic light scattering. Strong interaction upon ZIF-8 encapsulation caused demonstrable cell wall damage to B. breve and slightly reduced bacterial viability, delaying the growth of encapsulated bacteria. Cell wall damage and reduced viability did not occur upon encapsulation with weakly interacting yolk-shells. Only alginate-hydrogel-based shells yielded protection against simulated gastric acid and tetracycline. Accordingly, only alginate-hydrogel-encapsulated B. breve operated synergistically with tetracycline in killing tetracycline-resistant Escherichia coli adhering to intestinal epithelial layers and maintained surface coverage of transwell membranes by epithelial cell layers and their barrier integrity. This synergy between alginate-hydrogel-encapsulated B. breve and an antibiotic warrants further studies for treating antibiotic-resistant E. coli infections in the gastrointestinal tract

Visualization of Bacterial Colonization and Cellular Layers in a Gut-on-a-Chip System Using Optical Coherence Tomography

Imaging of cellular layers in a gut-on-a-chip system has been confined to two-dimensional (2D)-imaging through conventional light microscopy and confocal laser scanning microscopy (CLSM) yielding three-dimensional- and 2D-cross-sectional reconstructions. However, CLSM requires staining and is unsuitable for longitudinal visualization. Here, we compare merits of optical coherence tomography (OCT) with those of CLSM and light microscopy for visualization of intestinal epithelial layers during protection by a probiotic Bifidobacterium breve strain and a simultaneous pathogen challenge by an Escherichia coli strain. OCT cross-sectional images yielded film thicknesses that coincided with end-point thicknesses derived from cross-sectional CLSM images. Light microscopy on histological sections of epithelial layers at the end-point yielded smaller layer thicknesses than OCT and CLSM. Protective effects of B. breve adhering to an epithelial layer against an E. coli challenge included the preservation of layer thickness and membrane surface coverage by epithelial cells. OCT does not require staining or sectioning, making OCT suitable for longitudinal visualization of biological films, but as a drawback, OCT does not allow an epithelial layer to be distinguished from bacterial biofilms adhering to it. Thus, OCT is ideal to longitudinally evaluate epithelial layers under probiotic protection and pathogen challenges, but proper image interpretation requires the application of a second method at the end-point to distinguish bacterial and epithelial films

One-Dimensional Lateral Force Anisotropy at the Atomic Scale in Sliding Single Molecules on a Surface

Using a q+ atomic force microscopy at low temperature, a sexiphenyl molecule is slid across an atomically flat Ag(111) surface along the direction parallel to its molecular axis and sideways to the axis. Despite identical contact area and underlying surface geometry, the lateral force required to move the molecule in the direction parallel to its molecular axis is found to be about half of that required to move it sideways. The origin of the lateral force anisotropy observed here is traced to the one-dimensional shape of the molecule, which is further confirmed by molecular dynamics simulations. We also demonstrate that scanning tunneling microscopy can be used to determine the comparative lateral force qualitatively. The observed one-dimensional lateral force anisotropy may have important implications in atomic scale frictional phenomena on materials surfaces

The Nature of Optically Dull Active Galactic Nuclei in COSMOS

We present infrared, optical, and X-ray data of 48 X-ray bright, optically dull AGNs in the COSMOS field. These objects exhibit the X-ray luminosity of an active galactic nucleus (AGN) but lack broad and narrow emission lines in their optical spectrum. We show that despite the lack of optical emission lines, most of these optically dull AGNs are not well-described by a typical passive red galaxy spectrum: instead they exhibit weak but significant blue emission like an unobscured AGN. Photometric observations over several years additionally show significant variability in the blue emission of four optically dull AGNs. The nature of the blue and infrared emission suggest that the optically inactive appearance of these AGNs cannot be caused by obscuration intrinsic to the AGNs. Instead, up to ~70% of optically dull AGNs are diluted by their hosts, with bright or simply edge-on hosts lying preferentially within the spectroscopic aperture. The remaining ~30% of optically dull AGNs have anomalously high f_x/f_o ratios and are intrinsically weak, not obscured, in the optical. These optically dull AGNs are best described as a weakly accreting AGN with a truncated accretion disk from a radiatively inefficient accretion flow.Comment: 12 pages, 10 figures. Accepted for publication in the Ap

Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients [PIRATES]:A Phase I safety and feasibility trial of MRI-guided adaptive particle radiotherapy

Introduction: Radiation dose-escalation for head and neck cancer (HNC) patients aiming to improve cure rates is challenging due to the increased risk of unacceptable treatment-induced toxicities. With “Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients” (PIRATES), we present a novel treatment approach that is designed to facilitate dose-escalation while minimizing the risk of dose-limiting toxicities for locally advanced HPV-negative HNC patients. The aim of this Phase I trial is to assess the safety & feasibility of PIRATES approach. Methods: The PIRATES protocol employs a multi-faceted dose-escalation approach to minimize the risk of dose-limiting toxicities (DLTs): 1) sparing surrounding normal tissue from extraneous dose with intensity-modulated proton therapy, 2) mid-treatment hybrid hyper-fractionation for radiobiologic normal tissue sparing; 3) Magnetic Resonance Imaging (MRI) guided mid-treatment boost volume adaptation, and 4) iso-effective restricted organ-at-risk dosing to mucosa and bone tissues. The time-to-event Bayesian optimal interval (TITE-BOIN) design is employed to address the challenge of the long DLT window of 6 months and find the maximum tolerated dose. The primary endpoint is unacceptable radiation-induced toxicities (Grade 4, mucositis, dermatitis, or Grade 3 myelopathy, osteoradionecrosis) occurring within 6 months following radiotherapy. The second endpoint is any grade 3 toxicity occurring in 3–6 months after radiation. Discussion: The PIRATES dose-escalation approach is designed to provide a safe avenue to intensify local treatment for HNC patients for whom therapy with conventional radiation dose levels is likely to fail. PIRATES aims to minimize the radiation damage to the tissue surrounding the tumor volume with the combination of proton therapy and adaptive radiotherapy and within the high dose tumor volume with hybrid hyper-fractionation and not boosting mucosal and bone tissues. Ultimately, if successful, PIRATES has the potential to safety increase local control rates in HNC patients with high loco-regional failure risk. Trial registration: ClinicalTrials.gov ID: NCT04870840; Registration date: May 4, 2021. Netherlands Trial Register ID: NL9603; Registration date: July 15, 2021