Edge-weighting of gene expression graphs

In recent years, considerable research efforts have been directed to micro-array technologies and their role in providing simultaneous information on expression profiles for thousands of genes. These data, when subjected to clustering and classification procedures, can assist in identifying patterns and providing insight on biological processes. To understand the properties of complex gene expression datasets, graphical representations can be used. Intuitively, the data can be represented in terms of a bipartite graph, with weighted edges corresponding to gene-sample node couples in the dataset. Biologically meaningful subgraphs can be sought, but performance can be influenced both by the search algorithm, and, by the graph-weighting scheme and both merit rigorous investigation. In this paper, we focus on edge-weighting schemes for bipartite graphical representation of gene expression. Two novel methods are presented: the first is based on empirical evidence; the second on a geometric distribution. The schemes are compared for several real datasets, assessing efficiency of performance based on four essential properties: robustness to noise and missing values, discrimination, parameter influence on scheme efficiency and reusability. Recommendations and limitations are briefly discussed

A High-Throughput Mechanical Activator for Cartilage Engineering Enables Rapid Screening of in vitro Response of Tissue Models to Physiological and Supra-Physiological Loads

Articular cartilage is crucially influenced by loading during development, health, and disease. However, our knowledge of the mechanical conditions that promote engineered cartilage maturation or tissue repair is still incomplete. Current in vitro models that allow precise control of the local mechanical environment have been dramatically limited by very low throughput, usually just a few specimens per experiment. To overcome this constraint, we have developed a new device for the high throughput compressive loading of tissue constructs: the High Throughput Mechanical Activator for Cartilage Engineering (HiT-MACE), which allows the mechanoactivation of 6 times more samples than current technologies. With HiT-MACE we were able to apply cyclic loads in the physiological (e.g., equivalent to walking and normal daily activity) and supra-physiological range (e.g., injurious impacts or extensive overloading) to up to 24 samples in one single run. In this report, we compared the early response of cartilage to physiological and supra-physiological mechanical loading to the response to IL-1β exposure, a common but rudimentary in vitro model of cartilage osteoarthritis. Physiological loading rapidly upregulated gene expression of anabolic markers along the TGF-β1 pathway. Notably, TGF-β1 or serum was not included in the medium. Supra-physiological loading caused a mild catabolic response while IL-1β exposure drove a rapid anabolic shift. This aligns well with recent findings suggesting that overloading is a more realistic and biomimetic model of cartilage degeneration. Taken together, these findings showed that the application of HiT-MACE allowed the use of larger number of samples to generate higher volume of data to effectively explore cartilage mechanobiology, which will enable the design of more effective repair and rehabilitation strategies for degenerative cartilage pathologies

Megakaryocytic features useful for the diagnosis of myeloproliferative disorders can be obtained by a novel unsupervised software analysis

An unsupervised method for megakaryocyte detection and analysis is proposed, in order to validate supplementary tools which can be of help in supporting the pathologist in the classification of Philadelphia negative chronic myeloproliferative disorders with thrombocytosis. The experiment was conducted on high power magnification photomicrographs taken from hematoxylin-and-eosin 3 μm thick sections of formalin fixed, paraffin embedded bone marrow biopsies from patients with reactive thrombocytosis or chronic myeloproliferative disorders. Each megakaryocyte has been isolated in the photos through an image segmentation process, mainly based on mathematical morphology and wavelet analysis. A set of features (e.g. area, perimeter and fractal dimension of the cell and its nucleus, shape complexity via elliptic Fourier transform, and so on) is used to characterize the disorders and discriminate between essential thrombocythemia and idiopathic myelofibrosis. Features related to the general contour of the cell like cytoplasmic area and perimeter are good markers in distinguishing between normal or reactive and pathologic megakaryocytes while nuclear features and global circularity are helpful in the differential diagnosis between ET and prefibrotic IMF. The method proposed should be considered as a fast preprocessing tool for the diagnostic phase and its use can be extended to solve different object recognition problem

FLAME, a novel fuzzy clustering method for the analysis of DNA microarray data

BACKGROUND: Data clustering analysis has been extensively applied to extract information from gene expression profiles obtained with DNA microarrays. To this aim, existing clustering approaches, mainly developed in computer science, have been adapted to microarray data analysis. However, previous studies revealed that microarray datasets have very diverse structures, some of which may not be correctly captured by current clustering methods. We therefore approached the problem from a new starting point, and developed a clustering algorithm designed to capture dataset-specific structures at the beginning of the process. RESULTS: The clustering algorithm is named Fuzzy clustering by Local Approximation of MEmbership (FLAME). Distinctive elements of FLAME are: (i) definition of the neighborhood of each object (gene or sample) and identification of objects with "archetypal" features named Cluster Supporting Objects, around which to construct the clusters; (ii) assignment to each object of a fuzzy membership vector approximated from the memberships of its neighboring objects, by an iterative converging process in which membership spreads from the Cluster Supporting Objects through their neighbors. Comparative analysis with K-means, hierarchical, fuzzy C-means and fuzzy self-organizing maps (SOM) showed that data partitions generated by FLAME are not superimposable to those of other methods and, although different types of datasets are better partitioned by different algorithms, FLAME displays the best overall performance. FLAME is implemented, together with all the above-mentioned algorithms, in a C++ software with graphical interface for Linux and Windows, capable of handling very large datasets, named Gene Expression Data Analysis Studio (GEDAS), freely available under GNU General Public License. CONCLUSION: The FLAME algorithm has intrinsic advantages, such as the ability to capture non-linear relationships and non-globular clusters, the automated definition of the number of clusters, and the identification of cluster outliers, i.e. genes that are not assigned to any cluster. As a result, clusters are more internally homogeneous and more diverse from each other, and provide better partitioning of biological functions. The clustering algorithm can be easily extended to applications different from gene expression analysis

Multi-wavelength observations of the lensed quasar PKS 1830−-211 during the 2019 γ\gamma-ray flare

PKS 1830$-$211 is a $\gamma$-ray emitting, high-redshift (z $= 2.507 \pm 0.002$), lensed flat-spectrum radio quasar. During the period mid-February to mid-April 2019, this source underwent a series of strong $\gamma$-ray flares that were detected by both AGILE-GRID and Fermi-LAT, reaching a maximum $\gamma$-ray flux of $F_{\rm E>100 MeV}\approx 2.3\times10^{-5}$ ph cm$^{-2}$ s$^{-1}$. Here we report on a coordinated campaign from both on-ground (Medicina, OVRO, REM, SRT) and orbiting facilities (AGILE, Fermi, INTEGRAL, NuSTAR, Swift, Chandra), with the aim of investigating the multi-wavelength properties of PKS 1830$-$211 through nearly simultaneous observations presented here for the first time. We find a possible break in the radio spectra in different epochs above 15 GHz, and a clear maximum of the 15 GHz data approximately 110 days after the $\gamma$-ray main activity periods. The spectral energy distribution shows a very pronounced Compton dominance (> 200) which challenges the canonical one-component emission model. Therefore we propose that the cooled electrons of the first component are re-accelerated to a second component by, e.g., kink or tearing instability during the $\gamma$-ray flaring periods. We also note that PKS 1830$-$211 could be a promising candidate for future observations with both Compton satellites (e.g., e-ASTROGAM) and Cherenkov arrays (CTAO) which will help, thanks to their improved sensitivity, in extending the data availability in energy bands currently uncovered.Comment: Accepted for publication in MNRAS. 16 pages, 18 figures, 12 table

Complex variations of X-ray polarization in the X-ray pulsar LS V +44 17/RX J0440.9+4431

We report on \ixpe observations of the Be-transient X-ray pulsar LS V +44 17/RX J0440.9+4431 at two luminosity levels during the giant outburst in January--February 2023. Considering the observed spectral variability and changes in the pulse profiles, the source was likely caught in super- and sub-critical states with significantly different emission region geometry, associated with the presence of accretion columns and hot spots, respectively. We focus here on the pulse-phase resolved polarimetric analysis and find that the observed dependencies of the polarization degree and polarization angle (PA) on pulse phase are indeed drastically different for the two observations. The observed differences, if interpreted within the framework of the rotating vector model (RVM), imply dramatic variations of the spin axis inclination and the position angle and the magnetic colatitude by tens of degrees within just a few days separating the observations. We suggest that the apparent changes in the observed PA phase dependence are predominantly related to the presence of a polarized unpulsed component in addition to the polarized radiation associated with the pulsar itself. We show that the observed PA phase dependence in both observations can then be explained with a single set of RVM parameters defining the pulsar's geometry. We also suggest that the additional polarized component is likely produced by scattering of the pulsar radiation off the equatorial disk wind.Comment: 9 pages, 5 figures, submitted to A&

Complex variations in X-ray polarization in the X-ray pulsar LS V +44 17/RX J0440.9+4431

We report on Imaging X-ray polarimetry explorer (IXPE) observations of the Be-transient X-ray pulsar LS V +44 17/RX J0440.9+4431 made at two luminosity levels during the giant outburst in January- February 2023. Considering the observed spectral variability and changes in the pulse profiles, the source was likely caught in supercritical and subcritical states with significantly different emission-region geometry, associated with the presence of accretion columns and hot spots, respectively. We focus here on the pulse-phase-resolved polarimetric analysis and find that the observed dependencies of the polarization degree and polarization angle (PA) on the pulse phase are indeed drastically different for the two observations. The observed differences, if interpreted within the framework of the rotating vector model (RVM), imply dramatic variations in the spin axis inclination, the position angle, and the magnetic colatitude by tens of degrees within the space of just a few days. We suggest that the apparent changes in the observed PA phase dependence are predominantly related to the presence of an unpulsed polarized component in addition to the polarized radiation associated with the pulsar itself. We then show that the observed PA phase dependence in both observations can be explained with a single set of RVM parameters defining the pulsar s geometry. We also suggest that the additional polarized component is likely produced by scattering of the pulsar radiation in the equatorial disk wind

Polarized x-rays constrain the disk-jet geometry in the black hole x-ray binary Cygnus X-1

A black hole x-ray binary (XRB) system forms when gas is stripped from a normal star and accretes onto a black hole, which heats the gas sufficiently to emit x-rays. We report a polarimetric observation of the XRB Cygnus X-1 using the Imaging X-ray Polarimetry Explorer. The electric field position angle aligns with the outflowing jet, indicating that the jet is launched from the inner x-ray–emitting region. The polarization degree is 4.01 ± 0.20% at 2 to 8 kiloelectronvolts, implying that the accretion disk is viewed closer to edge-on than the binary orbit. These observations reveal that hot x-ray–emitting plasma is spatially extended in a plane perpendicular to, not parallel to, the jet axis

Uncovering the geometry of the hot X-ray corona in the Seyfert galaxy NGC 4151 with IXPE

We present an X-ray spectropolarimetric analysis of the bright Seyfert galaxy NGC 4151. The source has been observed with the Imaging X-ray Polarimetry Explorer (IXPE) for 700 ks, complemented with simultaneous XMM–Newton (50 ks) and NuSTAR (100 ks) pointings. A polarization degree Π = 4.9 ± 1.1 per cent and angle Ψ = 86° ± 7° east of north (68 per cent confidence level) are measured in the 2–8 keV energy range. The spectropolarimetric analysis shows that the polarization could be entirely due to reflection. Given the low reflection flux in the IXPE band, this requires, however, a reflection with a very large (>38 per cent) polarization degree. Assuming more reasonable values, a polarization degree of the hot corona ranging from ∼4 to ∼8 per cent is found. The observed polarization degree excludes a ‘spherical’ lamppost geometry for the corona, suggesting instead a slab-like geometry, possibly a wedge, as determined via Monte Carlo simulations. This is further confirmed by the X-ray polarization angle, which coincides with the direction of the extended radio emission in this source, supposed to match the disc axis. NGC 4151 is the first active galactic nucleus with an X-ray polarization measure for the corona, illustrating the capabilities of X-ray polarimetry and IXPE in unveiling its geometry