THO/TREX connects transcription with genome integrity in yeast, but a role of mammalian THO in these processes is uncertain, which suggests a differential implication of mRNP biogenesis factors in ...genome integrity in yeast and humans. We show that human THO depletion impairs transcription elongation and mRNA export and increases instability associated with DNA breaks, leading to hyper-recombination and γH2AX and 53BP1 foci accumulation. This is accompanied by replication alteration as determined by DNA combing. Genome instability is R-loop-dependent, as deduced from the ability of the AID enzyme to increase DNA damage and of RNaseH to reduce it, or from the enhancement of R-loop-dependent class-switching caused by THOC1-depletion in CH12 murine cells. Therefore, mammalian THO prevents R-loop formation and has a role in genome dynamics and function consistent with an evolutionary conservation of the functional connection between these mRNP biogenesis factors and genome integrity that had not been anticipated.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Silicon-substituted hydroxyapatite (SiHA) macroporous scaffolds have been prepared by robocasting. In order to optimize their bone regeneration properties, we have manufactured these scaffolds ...presenting different microstructures: nanocrystalline and crystalline. Moreover, their surfaces have been decorated with vascular endothelial growth factor (VEGF) to evaluate the potential coupling between vascularization and bone regeneration. In vitro cell culture tests evidence that nanocrystalline SiHA hinders pre-osteblast proliferation, whereas the presence of VEGF enhances the biological functions of both endothelial cells and pre-osteoblasts. The bone regeneration capability has been evaluated using an osteoporotic sheep model. In vivo observations strongly correlate with in vitro cell culture tests. Those scaffolds made of nanocrystalline SiHA were colonized by fibrous tissue, promoted inflammatory response and fostered osteoclast recruitment. These observations discard nanocystalline SiHA as a suitable material for bone regeneration purposes. On the contrary, those scaffolds made of crystalline SiHA and decorated with VEGF exhibited bone regeneration properties, with high ossification degree, thicker trabeculae and higher presence of osteoblasts and blood vessels. Considering these results, macroporous scaffolds made of SiHA and decorated with VEGF are suitable bone grafts for regeneration purposes, even in adverse pathological scenarios such as osteoporosis.
For the first time, the in vivo behavior of scaffolds made of silicon substituted hydroxyapatites (SiHA) has been evaluated under osteoporosis conditions. In order to optimize the bone regeneration properties of these bioceramics, 3D macroporous scaffolds have been manufactured by robocasting and implanted in osteoporotic sheep. Our experimental design shed light on the important issue of the biological response of nano-sized bioceramics vs highly crystalline bioceramics, as well as on the importance of coupling vascularization and bone growth processes by decorating SiHA scaffolds with vascular endothelial growth factor.
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ABSTRACT Understanding the nature of spiral structure in disk galaxies is one of the main, and still unsolved, questions in galactic astronomy. However, theoretical works are proposing new testable ...predictions whose detection is becoming feasible with recent development in instrumentation. In particular, streaming motions along spiral arms are expected to induce azimuthal variations in the chemical composition of a galaxy at a given galactic radius. In this Letter, we analyze the gas content in NGC 6754 with VLT/MUSE data to characterize its 2D chemical composition and H line of sight velocity distribution. We find that the trailing (leading) edge of the NGC 6754 spiral arms show signatures of tangentially slower, radially outward (tangentially faster, radially inward) streaming motions of metal-rich (poor) gas over a large range of radii. These results show direct evidence of gas radial migration for the first time. We compare our results with the gas behavior in an N-body disk simulation showing spiral morphological features rotating with a similar speed as the gas at every radius, in good agreement with the observed trend. This indicates that the spiral arm features in NGC 6754 may be transient and rotate similarly as the gas does at a large range of radii.
New precise results of a measurement of the elastic electron-proton scattering cross section performed at the Mainz Microtron MAMI are presented. About 1400 cross sections were measured with negative ...four-momentum transfers squared up to Q² = 1 (GeV/c)² with statistical errors below 0.2%. The electric and magnetic form factors of the proton were extracted by fits of a large variety of form factor models directly to the cross sections. The form factors show some features at the scale of the pion cloud. The charge and magnetic radii are determined to be <r²E>½ = 0.879(5)stat(4)syst(2)model(4)group fm and <r²M>½ = 0.777(13)stat(9)syst(5)model(2)group fm.
This work compares simulation and experimental results of the hydrodynamics of a two-dimensional, bubbling air-fluidized bed. The simulation in this study has been conducted using an ...Eulerian–Eulerian two-fluid approach based on two different and well-known closure models for the gas–particle interaction: the drag models due to Gidaspow and Syamlal & O'Brien. The experimental results have been obtained by means of Digital Image Analysis (DIA) and Particle Image Velocimetry (PIV) techniques applied on a real bubbling fluidized bed of 0.005
m thickness to ensure its two-dimensional behaviour. Several results have been obtained in this work from both simulation and experiments and mutually compared. Previous studies in literature devoted to the comparison between two-fluid models and experiments are usually focused on bubble behaviour (i.e. bubble velocity and diameter) and dense-phase distribution. However, the present work examines and compares not only the bubble hydrodynamics and dense-phase probability within the bed, but also the time-averaged vertical and horizontal component of the dense-phase velocity, the air throughflow and the instantaneous interaction between bubbles and dense-phase. Besides, quantitative comparison of the time-averaged dense-phase probability as well as the velocity profiles at various distances from the distributor has been undertaken in this study by means of the definition of a discrepancy factor, which accounts for the quadratic difference between simulation and experiments The resulting comparison shows and acceptable resemblance between simulation and experiments for dense-phase probability, and good agreement for bubble diameter and velocity in two-dimensional beds, which is in harmony with other previous studies. However, regarding the time-averaged velocity of the dense-phase, the present study clearly reveals that simulation and experiments only agree qualitatively in the two-dimensional bed tested, the vertical component of the simulated dense-phase velocity being nearly an order of magnitude larger than the one obtained from the PIV experiments. This discrepancy increases with the height above the distributor of the two-dimensional bed, and it is even larger for the horizontal component of the time-averaged dense-phase velocity. In other words, the results presented in this work indicate that the fine agreement commonly encountered between simulated and real beds on bubble hydrodynamics is not a sufficient condition to ensure that the dense-phase velocity obtained with two-fluid models is similar to that from experimental measurements on two-dimensional beds.
Context.
Controversial studies on the jet collimation profile of BL Lacertae (BL Lac), the eponymous blazar of the BL Lac objects class, complicate the scenario in this already puzzling class of ...objects. Understanding the jet geometry in connection with the jet kinematics and the physical conditions in the surrounding medium is fundamental for better constraining the formation, acceleration, and collimation mechanisms in extragalactic jets.
Aims.
With the aim of investigating the jet geometry in the innermost regions of the BL Lac jet, and resolving the controversy, we explore the radio jet in this source using high-resolution millimeter-wave VLBI data.
Methods.
We collect 86 GHz GMVA and 43 GHz VLBA data to obtain stacked images that we use to infer the jet collimation profile by means of two comparable methods. We analyze the kinematics at 86 GHz, and we discuss it in the context of the jet expansion. Finally, we consider a possible implication of the Bondi sphere in shaping the jet of BL Lac.
Results.
The jet in BL Lac expands with an overall conical geometry. A higher expanding rate region is observed between ∼5 and 10 pc (de-projected) from the black hole. Such a region is associated with the decrease in brightness usually observed in high-frequency VLBI images of BL Lac. The jet retrieves the original jet expansion around 17 pc, where the presence of a recollimation shock is supported by both the jet profile and the 15 GHz kinematics (MOJAVE survey). The change in the jet expansion profile occurring at ∼5 pc could be associated with a change in the external pressure at the location of the Bondi radius (∼3.3 × 10
5
R
S
).
Respiratory and heart rates are among the most important physiological parameters used to monitor patients' health. It is important to design devices that can measure these parameters without risking ...or altering the subject's health. In this context, a novel sensing method to monitor simultaneously the heartbeat and respiratory rate signals of patients within an electrically safety environment was developed and tested. An optical fiber-based sensor was used in order to detect two optical phenomena. Photo-plethysmography and the relation between bending radius and attenuation of optical fiber were coupled through a single beam light traveling along this fiber.
Background
COVID‐19 pandemic causes high global morbidity and mortality and better medical treatments to reduce mortality are needed.
Objective
To determine the added benefit of cyclosporine A (CsA), ...to low‐dose steroid treatment, in patients with COVID‐19.
Methods
Open‐label, non randomized pilot study of patients with confirmed infection of SARS‐CoV‐2 hospitalized from April to May 2020 at a single centre in Puebla, Mexico. Patients were assigned to receive either steroids or CsA plus steroids. Pneumonia severity was assessed by clinical, laboratory, and lung tomography. The death rate was evaluated at 28 days.
Results
A total of 209 adult patients were studied, 105 received CsA plus steroids (age 55.3 ± 13.3; 69% men), and 104 steroids alone (age 54.06 ± 13.8; 61% men). All patients received clarithromycin, enoxaparin and methylprednisolone or prednisone up to 10 days. Patient's death was associated with hypertension (RR = 3.5) and diabetes (RR = 2.3). Mortality was 22 and 35% for CsA and control groups (P = 0.02), respectively, for all patients, and 24 and 48.5% for patients with moderate to severe disease (P = 0.001). Higher cumulative clinical improvement was seen for the CsA group (Nelson Aalen curve, P = 0.001, log‐rank test) in moderate to severe patients. The Cox proportional hazard analysis showed the highest HR improvement value of 2.15 (1.39–3.34, 95%CI, P = 0.0005) for CsA treatment in moderate to severe patients, and HR = 1.95 (1.35–2.83, 95%CI, P = 0.0003) for all patients.
Conclusion
CsA used as an adjuvant to steroid treatment for COVID‐19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.
A massive, but light, Abelian U(1) gauge boson is a well-motivated possible signature of physics beyond the standard model of particle physics. In this Letter, the search for the signal of such a ...U(1) gauge boson in electron-positron pair production at the spectrometer setup of the A1 Collaboration at the Mainz Microtron is described. Exclusion limits in the mass range of 40 MeV/c^{2} to 300 MeV/c^{2}, with a sensitivity in the squared mixing parameter of as little as ε^{2}=8×10^{-7} are presented. A large fraction of the parameter space has been excluded where the discrepancy of the measured anomalous magnetic moment of the muon with theory might be explained by an additional U(1) gauge boson.
Purpose:
Knowing the contribution of neutron to collateral effects in treatments is both a complex and a mandatory task. This work aims to present an operative procedure for neutron estimates in any ...facility using a neutron digital detector.
Methods:
The authors’ previous work established a linear relationship between the total second cancer risk due to neutrons (TRn) and the number of MU of the treatment. Given that the digital detector also presents linearity with MU, its response can be used to determine the TRn per unit MU, denoted as m, normally associated to a generic Linac model and radiotherapy facility. Thus, from the number of MU of each patient treatment, the associated risk can be estimated. The feasibility of the procedure was tested by applying it in eight facilities; patients were evaluated as well.
Results:
From the reading of the detector under selected irradiation conditions, m values were obtained for different machines, ranging from 0.25 × 10−4% per MU for an Elekta Axesse at 10 MV to 6.5 × 10−4% per MU for a Varian Clinac at 18 MV. Using these values, TRn of patients was estimated in each facility and compared to that from the individual evaluation. Differences were within the range of uncertainty of the authors’ methodology of equivalent dose and risk estimations.
Conclusions:
The procedure presented here allows an easy estimation of the second cancer risk due to neutrons for any patient, given the number of MU of the treatment. It will enable the consideration of this information when selecting the optimal treatment for a patient by its implementation in the treatment planning system.
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