Re-epithelialization and immune cell behaviour in an ex vivo human skin model
A. Rakita, N. Nikolić, M. Mildner
et al.
A large body of literature is available on wound healing in humans. Nonetheless, a standardized ex vivo wound model without disruption of the dermal compartment has not been put forward with compelling justification. Here, we present a novel wound model based on application of negative pressure and its effects for epidermal regeneration and immune cell behaviour. Importantly, the basement membrane remained intact after blister roof removal and keratinocytes were absent in the wounded area. Upon six days of culture, the wound was covered with one to three-cell thick K14+Ki67+ keratinocyte layers, indicating that proliferation and migration were involved in wound closure. After eight to twelve days, a multi-layered epidermis was formed expressing epidermal differentiation markers (K10, filaggrin, DSG-1, CDSN). Investigations about immune cell-specific manners revealed more T cells in the blister roof epidermis compared to normal epidermis. We identified several cell populations in blister roof epidermis and suction blister fluid that are absent in normal epidermis which correlated with their decrease in the dermis, indicating a dermal efflux upon negative pressure. Together, our model recapitulates the main features of epithelial wound regeneration, and can be applied for testing wound healing therapies and investigating underlying mechanisms.
6587 sitasi
en
Chemistry, Medicine
SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo
K. P. Hui, J. Ho, Man-chun Cheung
et al.
Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19
Hin Chu, J. Chan, Yixin Wang
et al.
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus that has resulted in nearly 1,000,000 laboratory-confirmed cases including over 50,000 deaths. Although SARS-CoV-2 and SARS-CoV share a number of common clinical manifestations, SARS-CoV-2 appears to be highly efficient in person-to-person transmission and frequently cause asymptomatic infections. However, the underlying mechanism that confers these viral characteristics on high transmissibility and asymptomatic infection remain incompletely understood. Methods We comprehensively investigated the replication, cell tropism, and immune activation profile of SARS-CoV-2 infection in human lung tissues with SARS-CoV included as a comparison. Results SARS-CoV-2 infected and replicated in human lung tissues more efficiently than that of SARS-CoV. Within the 48-hour interval, SARS-CoV-2 generated 3.20 folds more infectious virus particles than that of SARS-CoV from the infected lung tissues (P<0.024). SARS-CoV-2 and SARS-CoV were similar in cell tropism, with both targeting types I and II pneumocytes, and alveolar macrophages. Importantly, despite the more efficient virus replication, SARS-CoV-2 did not significantly induce types I, II, or III interferons in the infected human lung tissues. In addition, while SARS-CoV infection upregulated the expression of 11 out of 13 (84.62%) representative pro-inflammatory cytokines/chemokines, SARS-CoV-2 infection only upregulated 5 of these 13 (38.46%) key inflammatory mediators despite replicating more efficiently. Conclusions Our study provided the first quantitative data on the comparative replication capacity and immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung tissues. Our results provided important insights on the pathogenesis, high transmissibility, and asymptomatic infection of SARS-CoV-2.
Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures
K. P. Hui, Man-chun Cheung, Ranawaka A.P.M Perera
et al.
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis. Methods We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls. Findings SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV. Interpretation The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens. Funding US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China.
A probabilistic atlas of the human thalamic nuclei combining ex vivo MRI and histology
J. E. Iglesias, R. Insausti, Garikoitz Lerma-Usabiaga
et al.
&NA; The human thalamus is a brain structure that comprises numerous, highly specific nuclei. Since these nuclei are known to have different functions and to be connected to different areas of the cerebral cortex, it is of great interest for the neuroimaging community to study their volume, shape and connectivity in vivo with MRI. In this study, we present a probabilistic atlas of the thalamic nuclei built using ex vivo brain MRI scans and histological data, as well as the application of the atlas to in vivo MRI segmentation. The atlas was built using manual delineation of 26 thalamic nuclei on the serial histology of 12 whole thalami from six autopsy samples, combined with manual segmentations of the whole thalamus and surrounding structures (caudate, putamen, hippocampus, etc.) made on in vivo brain MR data from 39 subjects. The 3D structure of the histological data and corresponding manual segmentations was recovered using the ex vivo MRI as reference frame, and stacks of blockface photographs acquired during the sectioning as intermediate target. The atlas, which was encoded as an adaptive tetrahedral mesh, shows a good agreement with previous histological studies of the thalamus in terms of volumes of representative nuclei. When applied to segmentation of in vivo scans using Bayesian inference, the atlas shows excellent test‐retest reliability, robustness to changes in input MRI contrast, and ability to detect differential thalamic effects in subjects with Alzheimer's disease. The probabilistic atlas and companion segmentation tool are publicly available as part of the neuroimaging package FreeSurfer.
489 sitasi
en
Computer Science, Medicine
Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids.
R. Jenkins, A. Aref, P. Lizotte
et al.
459 sitasi
en
Medicine, Biology
Does carbon pricing reduce emissions? A review of ex-post analyses
Jessica F. Green
Carbon pricing has been hailed as an essential component of any sensible climate policy. Internalize the externalities, the logic goes, and polluters will change their behavior. The theory is elegant, but has carbon pricing worked in practice? Despite a voluminous literature on the topic, there are surprisingly few works that conduct an ex-post analysis, examining how carbon pricing has actually performed. This paper provides a meta-review of ex-post quantitative evaluations of carbon pricing policies around the world since 1990. Four findings stand out. First, though carbon pricing has dominated many political discussions of climate change, only 37 studies assess the actual effects of the policy on emissions reductions, and the vast majority of these are focused on Europe. Second, the majority of studies suggest that the aggregate reductions from carbon pricing on emissions are limited—generally between 0% and 2% per year. However, there is considerable variation across sectors. Third, in general, carbon taxes perform better than emissions trading schemes (ETSs). Finally, studies of the EU-ETS, the oldest ETS, indicate limited average annual reductions—ranging from 0% to 1.5% per annum. For comparison, the IPCC states that emissions must fall by 45% below 2010 levels by 2030 in order to limit warming to 1.5 °C—the goal set by the Paris Agreement (Intergovernmental Panel on Climate Change 2018). Overall, the evidence indicates that carbon pricing has a limited impact on emissions.
335 sitasi
en
Physics, Economics
An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer
Paula Voabil, Marjolein J. W. de Bruijn, Lisanne M. Roelofsen
et al.
Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis
Alejandro Aguilera-Castrejon, Bernardo Oldak, Tom Shani
et al.
Transplantation of a human liver following 3 days of ex situ normothermic preservation
P. Clavien, P. Dutkowski, Matteo Mueller
et al.
Phenomenological mass model for exotic hadrons and predictions for masses of non-strange dibaryons as hexaquarks
Christoffer Beiming, Jesper Grönroos, Tommy Ohlsson
We investigate the mass spectra of exotic hadrons known as hexaquarks in the form of dibaryons. We use a phenomenological model based on an extended version of the Gürsey-Radicati mass formula for hadrons to include non-charmed baryons, charmed baryons, and non-strange dibaryons to be able to predict masses of potential dibaryon states. We perform six numerical fits of this model to input data for three different sets of masses of baryons and dibaryons. We find that the model can fit some of the data sets well, especially the sets including charmed baryons and non-strange dibaryons, and observe that the predicted mass of one of the dibaryons is close to the measured mass of the observed hexaquark candidate $d^*(2380)$ reported by the WASA-at-COSY experiment. The predicted mass of the deuteron is slightly larger than its measured mass. Finally, for the data sets including charmed baryon and non-strange dibaryon masses, we find that the predicted masses of potential dibaryon states are all in the range from 1900 MeV to 3700 MeV.
Study of proton capture resonant state of ^{15}O at 7556 keV
Sathi Sharma, Arkabrata Gupta, M. Roy Chowdhury
et al.
The slowest reaction in the CNO cycle 14N(p, gamma)15O has been studied by populating the E^lab_p =278 keV (E^r_c.m.=259 keV) proton capture resonant state of ^{15}O at 7556 keV. The strength of the resonance has been determined from the experimental data. The level lifetime of the sub-threshold resonant state at Ex=6792 keV, as well as the lifetimes of the 5181 keV and 6172 keV states, have been measured using the Doppler shift attenuation method (DSAM). The structural properties of the nucleus ^{15}O, such as, the level energies, transition strengths, level lifetimes, and spectroscopic factors, have been calculated theoretically by using the large basis shell model, which agrees reasonably well with the present as well as the previous experimental data.
Theoretical analysis of $^8$Li + $^{208}$Pb reaction and the critical angular momentum for complete fusion
Bahati Mukeru, Mantile L. Lekala, Jesus Lubian
et al.
In a theoretical approach, the complete and incomplete fusions are investigated by considering the $^8$Li+$^{208}$Pb reaction. By decreasing the projectile ground-state binding energy $\varepsilon_b$ from its known experimental value, the complete fusion is shown to have insignificant dependence on such variations, whereas the incomplete fusion strongly depends on that. The complete and incomplete fusion cross sections are calculated by using a combination of both continuum-discretized coupled-channel and sum-rule models. To this end, an incident-energy dependent cut-off angular momentum $L_c$ is first obtained by using the available complete fusion experimental data, within an approach which is extended to model results obtained for other incident-energies. An approximated fitted expression linking $L_c$ to the well-known critical value $L_{\rm crit}$ derived by Wilczyński [Nucl. Phys. A 216 (1973) 386] suggests a generalization of the corresponding sum-rule model to energies around and below the Coulomb barrier.
Comment on arXiv:1612.01502 'Is the Trineutron Resonance Lower in Energy than a Tetraneutron Resonance ?'
P. Truöl, J. P. MIller
Comment on the article by S. Gandolfi et al. Phys.Rev.Letters 118 (2017), 232501; arXiv:1612.01502 [nucl-th]
Intrinsic Fluctuations of the Proton Saturation Momentum Scale in High Multiplicity p+p Collisions
Larry McLerran, Prithwish Tribedy
High multiplicity events in p+p collisions are studied using the theory of the Color Glass Condensate. We show that intrinsic fluctuations of the proton saturation momentum scale are needed in addition to the sub-nucleonic color charge fluctuations to explain the very high multiplicity tail of distributions in p+p collisions. The origin of such intrinsic fluctuations are presumably non-perturbative in nature. Classical Yang Mills simulations using the IP-Glasma model are performed to make quantitative estimations. We find that fluctuations as large as $\cal O$(1) of the average values of the saturation momentum scale can lead to rare high multiplicity events seen in p+p data at RHIC and LHC energies. Using the available data on multiplicity distributions we try to constrain the distribution of the proton saturation momentum scale and make predictions for the multiplicity distribution in 13 TeV p+p collisions.
Transverse Spin Structure of the Nucleon
Matthias Grosse Perdekamp, Feng Yuan
We review the current status and future perspectives of theory and experiments of transverse spin phenomena in high-energy scattering processes off nucleon targets and related issues in nucleon structure and QCD. Systematic exploration of transverse spin effects requires measurements in polarized deep-inelastic scattering, polarized pp collisions, and e+e- annihilations. Sophisticated QCD-based techniques are also needed to analyze the experimental data sets.
Silica aerogel radiator for use in the A-RICH system utilized in the Belle II experiment
Makoto Tabata, Ichiro Adachi, Nao Hamada
et al.
This paper presents recent progress in the development and mass production of large-area hydrophobic silica aerogels for use as radiators in the aerogel-based ring-imaging Cherenkov (A-RICH) counter, which will be installed in the forward end cap of the Belle II detector. The proximity-focusing A-RICH system is especially designed to identify charged kaons and pions. The refractive index of the installed aerogel Cherenkov radiators is approximately 1.05, and we aim for a separation capability exceeding 4$σ$ at momenta up to 4 GeV/$c$. Large-area aerogel tiles (over 18 $\times $ 18 $\times $ 2 cm$^3$) were first fabricated in test productions by pin drying in addition to conventional methods. We proposed to fill the large end-cap region (area 3.5 m$^2$) with 124 water-jet-trimmed fan-shaped dual-layer-focusing aerogel combinations of different refractive indices (1.045 and 1.055). Guided by the test production results, we decided to manufacture aerogels by the conventional method and are currently proceeding with mass production. In an electron beam test undertaken at the DESY, we confirmed that the $K$/$π$ separation capability of a prototype A-RICH counter exceeded 4$σ$ at 4 GeV/$c$.
en
physics.ins-det, hep-ex
Pre-equilibrium α-particle emission as a probe to study α-clustering in nuclei
O. Fotina, S. Goncharov, D. Eremenko
et al.
A theoretical approach was developed to describe secondary particle emission in heavy ion collisions, with special regards to pre-equilibrium α-particle production. The probabilities of neutron, proton and α-particle emission have been evaluated for both the equilibrium and pre-equilibrium stages of the process. Effects due the possible cluster structure of the projectile which has been excited during the collisions have been experimentally evidenced studying the double differential cross sections of p and α-particles emitted in the E=250MeV 16 O + 116 Sn reaction. Calculations within the present model with different clusterization probabilities have been compared to the experimental data.
4 sitasi
en
Physics, Materials Science
X-ray radiographic technique for measuring density uniformity of silica aerogel
Makoto Tabata, Yoshikiyo Hatakeyama, Ichiro Adachi
et al.
This paper proposes a new X-ray radiographic technique for measuring density uniformity of silica aerogels used as radiator in proximity-focusing ring-imaging Cherenkov detectors. To obtain high performance in a large-area detector, a key characteristic of radiator is the density (i.e. refractive index) uniformity of an individual aerogel monolith. At a refractive index of n = 1.05, our requirement for the refractive index uniformity in the transverse plane direction of an aerogel tile is |δ(n - 1)/(n - 1)| < 4% in a focusing dual layer radiator (with different refractive indices) scheme. We applied the radiographic technique to evaluate the density uniformity of our original aerogels from a trial production and that of Panasonic products (SP-50) as a reference, and to confirm they have sufficient density uniformity within \pm 1% along the transverse plane direction. The measurement results show that the proposed technique can quantitatively estimate the density uniformity of aerogels.
en
physics.ins-det, hep-ex
Role of Sterile Neutrino Warm Dark Matter in Rhenium and Tritium Beta Decays
H. J. de Vega, O. Moreno, E. Moya de Guerra
et al.
Sterile neutrinos with mass in the range of one to a few keV are important as extensions of the Standard Model of particle physics and are serious dark matter (DM) candidates. This DM mass scale (warm DM) is in agreement with both cosmological and galactic observations. We study the role of a keV sterile neutrino through its mixing with a light active neutrino in Rhenium 187 and Tritium beta decays. We pinpoint the energy spectrum of the beta particle, 0 < T_e < (Q_{beta} - m_s), as the region where a sterile neutrino could be detected and where its mass m_s could be measured. This energy region is at least 1 keV away rom the region suitable to measure the mass of the light active neutrino, located near the endpoint Q_{beta} . The emission of a keV sterile neutrino in a beta decay could show up as a small kink in the spectrum of the emitted beta particle. With this in view, we perform a careful calculation of the Rhenium and Tritium beta spectra and estimate the size of this perturbation by means of the dimensionless ratio R of the sterile neutrino to the active neutrino contributions. We comment on the possibility of searching for sterile neutrino signatures in two experiments which are currently running at present, MARE and KATRIN, focused on the Rhenium 187 and Tritium beta decays respectively.