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Whole-genome doubling (WGD) is a recurrent event in human cancers and it promotes chromosomal instability and acquisition of aneuploidies1–8. However, the three-dimensional organization of chromatin in WGD cells and its contribution to oncogenic phenotypes are currently unknown. Here we show that in p53-deficient cells, WGD induces loss of chromatin segregation (LCS). This event is characterized by reduced segregation between short and long chromosomes, A and B subcompartments and adjacent chromatin domains. LCS is driven by the downregulation of CTCF and H3K9me3 in cells that bypassed activation of the tetraploid checkpoint. Longitudinal analyses revealed that LCS primes genomic regions for subcompartment repositioning in WGD cells. This results in chromatin and epigenetic changes associated with oncogene activation in tumours ensuing from WGD cells. Notably, subcompartment repositioning events were largely independent of chromosomal alterations, which indicates that these were complementary mechanisms contributing to tumour development and progression. Overall, LCS initiates chromatin conformation changes that ultimately result in oncogenic epigenetic and transcriptional modifications, which suggests that chromatin evolution is a hallmark of WGD-driven cancer.

Motivated by increased interest in experiments in which light appears to propagate by tunnelling at superluminal velocity, the Lorentz invariant theory proposed by Partha Ghose to explain these surprising effects is revisited. This theory is based on the Harish-Chandra formalism, which describes the relativistic dynamics of a massless spin-1 boson, like a photon. Via this formalism, the Bohmian average transport velocity of the electromagnetic energy is formulated. It is proved that, if the dielectric making the waveguide is nonabsorptive and nondispersive, this velocity can be superluminal. This result is validated in the framework of quantum electrodynamics, demonstrating that the average velocity of the photon inside the waveguide is given by the contribution of instantaneous superluminal velocities. This theory, therefore, suggests the optimal conditions for designing optical devices capable of locally transporting electromagnetic energy at superluminal velocities mitigating the signal attenuation., 19 pages

In this study, the Schrodinger equation of a valence electron in a periodic crystal potential is formulated and solved using the elliptic function formalism. The method allows double periodic lattice planes to be represented in the Gauss plane. The reality of the obtained eigenfunctions and the structure of the valence and conduction bands are also investigated., 11 pages, this is the preprint of the accepted manuscript

Background Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by specific vascular and obstetric manifestations and by antiphospholipid antibodies (aPL) positivity. Microvascular damage in the course of APS and “aPL carrier” patients without symptoms is poorly investigated. Objectives This study aims to compare nailfold videocapillaroscopy (NVC) microvascular parameters in APS patients and non-symptomatic "aPL carriers" and to investigate their possible correlations with different aPL subtypes. Methods NVC was performed during standard evaluations in 18 APS patients (mean age 50 ± 13.8 years), 24 "aPL carriers" without symptoms (mean age 46.4 ± 16.4 years), and 18 control patients (CTR) (mean age 74 ± 12.5 years) taking oral anticoagulants for non-immunological indications (i.e., cardiovascular accidents). All patients were investigated for the presence of dilated capillaries, giant capillaries, microhemorrhages, capillary loss, and further non-specific/specific abnormalities (i.e., branched “bushy” capillaries, sign of neoangiogenesis) by NVC. Every alteration was also classified according to a semi-quantitative score. Lupus anticoagulant, anticardiolipin antibodies, and antibeta2 glycoprotein I antibodies were tested in each patient. Results APS patients showed at NVC increased frequency of microhemorrhages (p = 0.039)—particularly a “comb-like” pattern (parallel hemorrhages) (p = 0.002)—than "aPL carriers". Of note, there were no significant differences concerning the isolated number of microhemorrhages between APS and the CTR group (p = 0.314), but “comb-like” hemorrhages were significantly more frequent in the APS group (p = 0.034). Not any significant correlation was found between the aPL subtypes and NVC parameters. Conclusions APS patients showed significantly a greater number of non-specific NVC abnormalities than "aPL carriers", particularly the “comb-like” NVC pattern. Oral anticoagulants may represent a confounding factor for isolated microhemorrhages. Not any correlation was found between aPL subtypes and NVC parameters. Further investigations are needed to better characterize the microvascular endothelium damage induced by aPL.

In this study the tachyon-like Dirac equation, formulated by Chodos to describe superluminal neutrino, is solved. The analytical solutions are Gaussian wave packets obtained using the envelope method. It is shown that the superluminal neutrino behaves like a pseudo-tachyon, namely a particle with subluminal velocity and pure imaginary mass that fulfils the energy-momentum relation typical of classical tachyons. The obtained results are used to prove that the trembling motion of the particle position around the median, known as Zitterbewegung, also takes place for the superluminal neutrino, even if the oscillation velocity is always lower than the speed of light. Finally, the pseudo-tachyon wave packet is used to calculate the probability of oscillation between mass states, obtaining a formula analogous to the one obtained for the ordinary neutrino. This suggest that in the experiments concerning neutrino oscillation is not possible to distinguish tachyonic neutrinos from ordinary ones., 11 pages, 2 figures

In this paper, we revisit the two theoretical approaches for the formulation of the tachyonic Dirac equation. The first approach works within the theory of restricted relativity, starting from a Lorentz invariant Lagrangian consistent with a spacelike four-momentum. The second approach uses the theory of relativity extended to superluminal motions and works directly on the ordinary Dirac equation through superluminal Lorentz transformations. The equations resulting from the two approaches show mostly different, if not opposite, properties. In particular, the first equation violates the invariance under the action of the parity and charge conjugation operations. Although it is a good mathematical tool to describe the dynamics of a space-like particle, it also shows that the mean particle velocity is subluminal. In contrast, the second equation is invariant under the action of parity and charge conjugation symmetries, but the particle it describes is consistent with the classical dynamics of a tachyon. This study shows that it is not possible with the currently available theories to formulate a covariant equation that coherently describes the neutrino in the framework of the physics of tachyons, and depending on the experiment, one equation rather than the other should be used., Comment: 14 pages

We investigate the important clinical problem of predicting prognosis-related breast cancer molecular subtypes using whole-transcriptome information present in The Cancer Genome Atlas Project (TCGA) dataset. From a Machine Learning perspective, the data is both high-dimensional with over nineteen thousand features, and extremely small with only about one thousand labeled instances in total. To deal with the dearth of information we compare classical, deep and semi-supervised learning approaches on the subtyping task. Specifically, we compare a L\(_1\)-regularized Logistic Regression, a 2-hidden layer Feed Forward Neural Network and a Variational Autoencoder based semi-supervised learner that makes use of pan-cancer TCGA data as well as normal breast tissue data from a second source. We find that the classical supervised technique performs at least as well as the deep and semi-supervised learning approaches, although learning curve analysis suggests that insufficient unlabeled data may be being provided for the chosen semi-supervised learning technique to be effective.

Topologically associated domains (TADs) are defined as regions of self-interaction. To date, it is unclear how to reconcile TAD structure with CTCF site orientation, which is known to coordinate chromatin loops anchored by Cohesin rings at convergent CTCF site pairs. We first approached this problem by 4C analysis of the FKBP5 locus. This uncovered a CTCF loop encompassing FKBP5 but not its entire TAD. However, adjacent CTCF sites were able to form ‘back-up’ loops and these were located at TAD boundaries. We then analysed the spatial distribution of CTCF patterns along the genome together with a boundary identity conservation ‘gradient’ obtained from primary blood cells. This revealed that divergent CTCF sites are enriched at boundaries and that convergent CTCF sites mark the interior of TADs. This conciliation of CTCF site orientation and TAD structure has deep implications for the further study and engineering of TADs and their boundaries.

In this study, a novel theory to investigate the mass oscillation of particles is proposed. It has been proven that, at high-energy conditions, the fermion field described by Dirac Lagrangian interacts with the half-integer spin tachyon field with negative energy, causing the formation of composite particles whose mass depends on the total angular momentum. The proposed theory is based on a new interpretation of the Majorana equation for particles with arbitrary spin and shows that mass oscillation is a phenomenon in which the component of particle decay prevails over that of mixing mass states. Using the kinematic of Lemke for spacelike particle decay, we propose a mechanism able to explain the neutrino flavour change. The proposed mechanism is also investigated concerning the shape of its spectrum. Finally, the Lagrangian field of composite particles is formulated., Comment: 18 pages, 1 figure

Most scientific databases consist of datasets (or sources) which in turn include samples (or files) with an identical structure (or schema). In many cases, samples are associated with rich metadata, describing the process that leads to building them (e.g.: the experimental conditions used during sample generation). Metadata are typically used in scientific computations just for the initial data selection; at most, metadata about query results is recovered after executing the query, and associated with its results by post-processing. In this way, a large body of information that could be relevant for interpreting query results goes unused during query processing. In this paper, we present ScQL, a new algebraic relational language, whose operations apply to objects consisting of data–metadatapairs, by preserving such one-to-one correspondence throughout the computation. We formally define each operation and we describe an optimization, called meta-first, that may significantly reduce the query processing overhead by anticipating the use of metadata for selectively loading into the execution environment only those input samples that contribute to the result samples. In ScQL, metadata have the same relevance as data, and contribute to building query results; in this way, the resulting samples are systematically associated with metadata about either the specific input samples involved or about query processing, thereby yielding a new form of metadata provenance. We present many examples of use of ScQL, relative to several application domains, and we demonstrate the effectiveness of the meta-first optimization.

Next Generation Sequencing is a 10-year old technology for reading the DNA, capable of producing massive amounts of genomic data - in turn, reshaping genomic computing. In particular, tertiary data analysis is concerned with the integration of heterogeneous regions of the genome; this is an emerging and increasingly important problem of genomic computing, because regions carry important signals and the creation of new biological or clinical knowledge requires the integration of these signals into meaningful messages. We specifically focus on how the GeCo project is contributing to tertiary data analysis, by overviewing the main results of the project so far and by describing its future scenarios.

Human parvovirus B19 infection in adults shows some clinical features similar to those found in autoimmune connective tissue diseases. To better clarify the relationship between viral infection and autoimmunity, we have evaluated the ability of anti-parvovirus antibodies to specifically recognize autoantigens in ten patients with chronic symmetric arthritis resembling rheumatoid arthritis or with recurrent episodes of arthritis and cutaneous manifestations and persistence of specific IgM antibodies against B19 parvovirus. We synthetized a 24-amino acid immunodominant peptide corresponding to a part of the virus protein 1 and virus protein 2 overlapping region. The peptide has been used to test patients' sera at different time points with an enzyme-linked immunosorbent assay (ELISA) and to purify anti-virus antibodies by affinity chromatography on a peptide-Sepharose column. Eluted immunoglobulins recognized the B19 peptide in both direct and competitive ELISA. Affinity-purified anti-parvovirus antibodies were then tested on a panel of autoantigens including human keratin, collagen type II, thyreoglobulin, single-strand (ss)DNA, cardiolipin and ribonucleoprotein antigen Sm. Eluted antibodies specifically recognized keratin, collagen type II, ssDNA and cardiolipin. Autoantibody activity was not detected in the immunoglobulin fraction after complete removal of anti-peptide antibodies and in antibodies eluted from normal donors. Epstein-Barr virus-transformed cell clones obtained from two subjects produced antibodies which simultaneously recognize the viral peptide and several autoantigens. To further confirm the role of the virus in inducing an autoantibody response, eight BALB/c mice were immunized with the viral peptide coupled to a carrier protein. Autoantibody activity against keratin, collagen II, cardiolipin and ssDNA was detected in six of the eight mice which developed a strong anti-virus response. Together, these data indicate that B19 parvovirus may be linked to the induction of an autoimmune response.

A hydrolytic side reaction in hydrated iridium chloride films heat-treated on titanium supports was discovered by simultaneous thermal analysis, emission FTIR and SIMS techniques. In the presence of water vapour the degree of hydrolysis increases significantly in the outermost part of the film leading to the formation of oxidic species at low temperatures. In a wet oxygen atmosphere encapsulated hydrogen chloride as a hydrolysis product reacts with the support to form titanium chloride species segregated in the surface region of the coating. In addition to the formation of hydrolysis products, the presence of surface species like iridium carbonyl and iridium carboxylate was also confirmed in the coating.

p40 was previously described as a regulatory molecule capable of inhibiting both the natural and the CD16-mediated cytotoxicity of NK cells. In this study, we analyze the effect of p40 molecule engagement on the NK cell triggering induced by activating HLA class I-specific NK receptors (NKR) or on TCR alpha beta-mediated T cell activation. CD3-CD16+ NK cell clones expressing activating NKR (either CD94 or p50) were analyzed in a redirected killing assay using P815 target cells and appropriate mAb. A strong target cell lysis was detected in the presence of anti-NKR or anti-CD16 mAb alone. Addition of anti-p40 mAb resulted in a strong inhibition of both anti-NKR or anti-CD16 mAb-induced cytolysis. mAb specific for either CD45 or lymphocyte function associated antigen-1 did not exert any inhibitory effect in the same experimental system. Free intracellular calcium ([Ca2+]i) increase induced by mAb cross-linking of activating CD94 or p50 was inhibited by simultaneous engagement of p40 molecules, but not of other NK surface molecules including CD44 and CD56. In addition, cross-linking of p40 molecules strongly inhibited the CD94-induced tumor necrosis factor-alpha and IFN-gamma production. Analysis of TCR alpha beta or gamma delta T cell clones revealed that the engagement of p40 molecules, using specific mAb, induced some degree of inhibition only on anti-V beta (but not anti-V delta or anti-CD3) mAb-induced cytotoxicity. On the other hand, the p40 molecule engagement prevented T cell proliferation induced by either anti-V beta 8 or anti-V delta 2 mAb. A similar inhibitory effect was found on the IL-2-induced NK cell proliferation. Taken together, our present findings suggest that p40 may play a role in the regulation of NK and T lymphocyte activation and proliferation.

In this paper are presented data on the preparation and characterization of different oxide electrodes. RuO2–TiO2, IrO2–TiO2, and SnO2–Sb2O5 mixed-oxide films have been taken as model systems. For the first, the traditional preparation method based on the pyrolysis of precursor salt deposits was adopted. For the SnO2-based films, the spray pyrolysis preparation has been used. The characterization of RuO2–TiO2 films confirms the existence of a solid solution between the two component oxides over a wide composition range. Rutherford backscattering spectrometry confirms the occurrence of segregation of titanium oxide species in the outermost part of the films. Nuclear reaction analysis indicates that large amounts of carbon and hydrogen impurities are trapped in the oxide films. SnO2-based films were found to be less porous and chemically more simple. The differences between the two systems have been discussed in terms of the preparation method and the differences in chemical properties of the precursors. Keywords: oxide film electrodes, mixed-oxide films, Rutherford backscattering spectrometry, nuclear reaction analysis.

Motivation The relationship between gene co-expression and chromatin conformation is of great biological interest. Thanks to high-throughput chromosome conformation capture technologies (Hi-C), researchers are gaining insights on the tri-dimensional organization of the genome. Given the high complexity of Hi-C data and the difficult definition of gene co-expression networks, the development of proper computational tools to investigate such relationship is rapidly gaining the interest of researchers. One of the most fascinating questions in this context is how chromatin topology correlates with gene co-expression and which physical interaction patterns are most predictive of co-expression relationships. Results To address these questions, we developed a computational framework for the prediction of co-expression networks from chromatin conformation data. We first define a gene chromatin interaction network where each gene is associated to its physical interaction profile; then, we apply two graph embedding techniques to extract a low-dimensional vector representation of each gene from the interaction network; finally, we train a classifier on gene embedding pairs to predict if they are co-expressed. Both graph embedding techniques outperform previous methods based on manually designed topological features, highlighting the need for more advanced strategies to encode chromatin information. We also establish that the most recent technique, based on random walks, is superior. Overall, our results demonstrate that chromatin conformation and gene regulation share a non-linear relationship and that gene topological embeddings encode relevant information, which could be used also for downstream analysis. Availability and implementation The source code for the analysis is available at: https://github.com/marcovarrone/gene-expression-chromatin. Supplementary information Supplementary data are available at Bioinformatics online.