Integrin-independent movement of immune cells

Cell motility requires the temporal and spatial coordination of the actin cytoskeleton with cell-matrix adhesions. Since their discovery more than 20 years ago, integrins have been at the center of cell-matrix adhesion research. Integrin-mediated adhesions link the actin network to the extracellular matrix and are commonly observed as cells migrate across rigid two-dimensional substrates. However, as more cell motility studies are being conducted in three-dimensional (3D) culture systems and in vivo, the role of integrins has become less clear. Recent work has shown that leukocyte migration in 3D contexts can be integrin-independent and that alternative mechanisms of cell adhesion are employed

First Evidence of a Precessing Jet Excavating a Protostellar Envelope

We present new, sensitive, near-infrared images of the Class I protostar, Elias 29, in the Ophiuchus cloud core. To explore the relationship between the infall envelope and the outflow, narrowband H2 1-0 S(1), Br-gamma, and narrowband K-continuum filters were used to image the source with the Wide-Field Infrared Camera on the Hale 5m telescope and with Persson's Auxiliary Nasmyth Infrared Camera on the Baade 6.5 m telescope. The source appears as a bipolar, scattered light nebula, with a wide opening angle in all filters, as is typical for late-stage protostars. However, the pure H2 emission-line images point to the presence of a heretofore undetected precessing jet. It is argued that high-velocity, narrow, precessing jets provide the mechanism for creating the observed wide-angled outflow cavity in this source.Comment: 11 pages, 1 figure, 1 tabl

Application of digital pathology-based advanced analytics of tumour microenvironment organisation to predict prognosis and therapeutic response.

In recent years, the application of advanced analytics, especially artificial intelligence (AI), to digital H&E images, and other histological image types, has begun to radically change how histological images are used in the clinic. Alongside the recognition that the tumour microenvironment (TME) has a profound impact on tumour phenotype, the technical development of highly multiplexed immunofluorescence platforms has enhanced the biological complexity that can be captured in the TME with high precision. AI has an increasingly powerful role in the recognition and quantitation of image features and the association of such features with clinically important outcomes, as occurs in distinct stages in conventional machine learning. Deep-learning algorithms are able to elucidate TME patterns inherent in the input data with minimum levels of human intelligence and, hence, have the potential to achieve clinically relevant predictions and discovery of important TME features. Furthermore, the diverse repertoire of deep-learning algorithms able to interrogate TME patterns extends beyond convolutional neural networks to include attention-based models, graph neural networks, and multimodal models. To date, AI models have largely been evaluated retrospectively, outside the well-established rigour of prospective clinical trials, in part because traditional clinical trial methodology may not always be suitable for the assessment of AI technology. However, to enable digital pathology-based advanced analytics to meaningfully impact clinical care, specific measures of 'added benefit' to the current standard of care and validation in a prospective setting are important. This will need to be accompanied by adequate measures of explainability and interpretability. Despite such challenges, the combination of expanding datasets, increased computational power, and the possibility of integration of pre-clinical experimental insights into model development means there is exciting potential for the future progress of these AI applications. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

A close look into the carbon disk at the core of the planetary nebula CPD-568032

We present high spatial resolution observations of the dusty core of the Planetary Nebula with Wolf-Rayet central star CPD-568032. These observations were taken with the mid-infrared interferometer VLTI/MIDI in imaging mode providing a typical 300 mas resolution and in interferometric mode using UT2-UT3 47m baseline providing a typical spatial resolution of 20 mas. The visible HST images exhibit a complex multilobal geometry dominated by faint lobes. The farthest structures are located at 7" from the star. The mid-IR environment of CPD-568032 is dominated by a compact source, barely resolved by a single UT telescope in a 8.7 micron filter. The infrared core is almost fully resolved with the three 40-45m projected baselines ranging from -5 to 51 degree but smooth oscillating fringes at low level have been detected in spectrally dispersed visibilities. This clear signal is interpreted in terms of a ring structure which would define the bright inner rim of the equatorial disk. Geometric models allowed us to derive the main geometrical parameters of the disk. For instance, a reasonably good fit is reached with an achromatic and elliptical truncated Gaussian with a radius of 97+/-11 AU, an inclination of 28+/-7 degree and a PA for the major axis at 345+/-7 degree. Furthermore, we performed some radiative transfer modeling aimed at further constraining the geometry and mass content of the disk, by taking into account the MIDI dispersed visibilities, spectra, and the large aperture SED of the source. These models show that the disk is mostly optically thin in the N band and highly flared.Comment: Paper accepted in A&

Equatorial ozone characteristics as measured at Natal (5.9 deg S, 35.2 deg W)

Ozone density profiles obtained through electrochemical concentration cell (ECC) sonde measurements at Natal were analyzed. Time variations, as expected, are small. Outstanding features of the data are tropospheric densities substantially higher than those measured at other stations, and also a total ozone content that is higher than the averages given by satellite measurements

FARS2 mutations presenting with pure spastic paraplegia and lesions of the dentate nuclei.

Mutations in FARS2, the gene encoding the mitochondrial phenylalanine-tRNA synthetase (mtPheRS), have been linked to a range of phenotypes including epileptic encephalopathy, developmental delay, and motor dysfunction. We report a 9-year-old boy with novel compound heterozygous variants of FARS2, presenting with a pure spastic paraplegia syndrome associated with bilateral signal abnormalities in the dentate nuclei. Exome sequencing identified a paternal nonsense variant (Q216X) lacking the catalytic core and anticodon-binding regions, and a maternal missense variant (P136H) possessing partial enzymatic activity. This case confirms and expands the phenotype related to FARS2 mutations with regards to clinical presentation and neuroimaging findings

Hydrodynamical simulations of the jet in the symbiotic star MWC 560 III. Application to X-ray jets in symbiotic stars

In papers I and II in this series, we presented hydrodynamical simulations of jet models with parameters representative of the symbiotic system MWC 560. These were simulations of a pulsed, initially underdense jet in a high density ambient medium. Since the pulsed emission of the jet creates internal shocks and since the jet velocity is very high, the jet bow shock and the internal shocks are heated to high temperatures and should therefore emit X-ray radiation. In this paper, we investigate in detail the X-ray properties of the jets in our models. We have focused our study on the total X-ray luminosity and its temporal variability, the resulting spectra and the spatial distribution of the emission. Temperature and density maps from our hydrodynamical simulations with radiative cooling presented in the second paper are used together with emissivities calculated with the atomic database ATOMDB. The jets in our models show extended and variable X-ray emission which can be characterized as a sum of hot and warm components with temperatures that are consistent with observations of CH Cyg and R Aqr. The X-ray spectra of our model jets show emission line features which correspond to observed features in the spectra of CH Cyg. The innermost parts of our pulsed jets show iron line emission in the 6.4 - 6.7 keV range which may explain such emission from the central source in R Aqr. We conclude that MWC 560 should be detectable with Chandra or XMM-Newton, and such X-ray observations will provide crucial for understanding jets in symbiotic stars.Comment: 10 pages, 12 figures, accepted for publication in ApJ, uses emulateap

Observational Study of the Multistructured Planetary Nebula NGC 7354

We present an observational study of the planetary nebula (PN) NGC 7354 consisting of narrowband Halpha and [NII]6584 imaging as well as low- and high-dispersion long-slit spectroscopy and VLA-D radio continuum. According to our imaging and spectroscopic data, NGC 7354 has four main structures: a quite round outer shell and an elliptical inner shell, a collection of low-excitation bright knots roughly concentrated on the equatorial region of the nebula, and two symmetrical jet-like features, not aligned either with the shells' axes, or with each other. We have obtained physical parameters like electron temperature and electron density as well as ionic and elemental abundances for these different structures. Electron temperature and electron density slightly vary throughout the nebula. The local extinction coefficient c_Hbeta shows an increasing gradient from south to north and a decreasing gradient from east to west consistent with the number of equatorial bright knots present in each direction. Abundance values show slight internal variations but most of them are within the estimated uncertainties. In general, abundance values are in good agreement with the ones expected for PNe. Radio continuum data are consistent with optically thin thermal emission. We have used the interactive three-dimensional modeling tool SHAPE to reproduce the observed morphokinematic structures in NGC 7354 with different geometrical components. Our SHAPE model is in very good agreement with our imaging and spectroscopic observations. Finally, after modeling NGC 7354 with SHAPE, we suggest a possible scenario for the formation of the nebula.Comment: Accepted for publication in AJ, 12 pages, 8 figure