This package can be used to compute associations among genes (gene-networks) or between genes and some external traits (i.e. clinical).

This package predicts the gene-gene interaction network and identifies the direct transcriptional targets of the perturbation using an ODE (Ordinary Differential Equation) based method.

eudysbiome a package that permits to annotate the differential genera as harmful/harmless based on their ability to contribute to host diseases (as indicated in literature) or unknown based on their ambiguous genus classification. Further, the package statistically measures the eubiotic (harmless genera increase or harmful genera decrease) or dysbiotic(harmless genera decrease or harmful genera increase) impact of a given treatment or environmental change on the (gut-intestinal, GI) microbiome in comparison to the microbiome of the reference condition.

In Alicandro et al. (J Mech Phys Solids 92:87-104, 2016) a simple discrete scheme for the motion of screw dislocations toward low energy configurations has been proposed. There, a formal limit of such a scheme, as the lattice spacing and the time step tend to zero, has been described. The limiting dynamics agrees with the maximal dissipation criterion introduced in Cermelli and Gurtin (Arch Ration Mech Anal 148, 1999) and predicts motion along the glide directions of the crystal. In this paper, we provide rigorous proofs of the results in [3], and in particular of the passage from the discrete to the continuous dynamics. The proofs are based on ? -convergence techniques.

We show that minimizers of the Heitmann-Radin energy (Heitmann and Radin in J Stat Phys 22(3): 281-287, 1980) are unique if and only if the particle number N belongs to an infinite sequence whose first thirty-five elements are 1, 2, 3, 4, 5, 7, 8, 10, 12, 14, 16, 19, 21, 24, 27, 30, 33, 37, 40, 44, 48, 52, 56, 61, 65, 70, 75, 80, 85, 91, 96, 102, 108, 114, 120 (see the paper for a closed-form description of this sequence). The proof relies on the discrete differential geometry techniques introduced in De Luca and Friesecke (Crystallization in two dimensions and a discrete Gauss-Bonnet Theorem, 2016).

Additionally, it has also come to light an implication of the mitochondrial genome in the regulation of the intracellular epigenetic landscape, as demonstrated by the being itself object of epigenetic modifications. An increasing body of data is progressively indicating that the comprehension of the epigenetic landscape, actively integrated with the genetic elements, is crucial to delineate the molecular basis of the inter-individual complexity of ageing process. Indeed, it has emerged that DNA methylation changes occur during ageing, consisting mainly in a progressive process of genome demethylation, in a hypermethylation of gene-specific CpG dinucleotides, as well as in an inter-individual divergence of the epigenome due to stochastic events and environmental exposures throughout life, namely as epigenetic drift.

Degeneration is a hallmark of autoimmune diseases, whose incidence grows worldwide. Currenttherapies attempt to control the immune response to limit degeneration, commonly promotingimmunodepression. Differently, mechanical stimulation is known to trigger healing (regeneration) andit has recently been proposed locally for its therapeutic potential on severely injured areas. As the earlystages of healing consist of altered intra- and inter-cellular fluxes of soluble molecules, we explored thepotential of this early signal to spread, over time, beyond the stimulation district and become systemic,to impact on distributed or otherwise unreachable injured areas. We report in a model of arthritis inrats how stimulations delivered in the subcutaneous dorsal tissue result, over time, in the control andhealing of the degeneration of the paws' joints, concomitantly with the systemic activation of woundhealing phenomena in blood and in correlation with a more eubiotic microbiome in the gut intestinaldistrict.

To exploit this stability and reinforce it, we conducted a meta-analysis on publicly available DNA methylation datasets generated on: normal colorectal, adenoma (ADE) and adenocarcinoma (CRC) samples using the Illumina 450k array, in the systems medicine frame, searching for tumor gene episignatures, to produce a carefully selected list of potential drivers, markers and targets of the disease. The analysis proceeds from a differential meta-analysis of the methylation profiles using an analytical pipeline recently developed by our group [1], through network reconstruction, topological and functional analyses, to finally highlight relevant epigenomic features. Our results show that genes already highlighted for their genetic or transcriptional alteration in colorectal cancer are also differentially methylated, reinforcing-regardless of the level of cellular control-their role in the complex of alterations involved in tumorigenesis. Colorectal cancer is among the leading causes of cancer death worldwide. Despite numerous molecular characterizations of the phenomenon, the exact dynamics of its onset and progression remain elusive. Colorectal cancer onset has been characterized by changes in DNA methylation profiles, that, owing to the stability of their patterns, are promising candidates to shed light on the molecular events laying at the base of this phenomenon.

This package has been developed to evaluate cellular engineering processes for direct differentiation of stem cells or conversion (transdifferentiation) of somatic cells to primary cells based on high throughput gene expression data screened either by DNA microarray or RNA sequencing. The package takes gene expression profiles as inputs from three types of samples: (i) somatic or stem cells to be (trans)differentiated (input of the engineering process), (ii) induced cells to be evaluated (output of the engineering process) and (iii) target primary cells (reference for the output). The package performs differential gene expression analysis for each pair-wise sample comparison to identify and evaluate the transcriptional differences among the 3 types of samples (input, output, reference). The ideal goal is to have induced and primary reference cell showing overlapping profiles, both very different from the original cells.

Searching and retrieving information from the Web is a primary activity needed to monitor the development and usage of Web resources. Possible benefits include improving user experience (e.g. by optimizing query results) and enforcing data/user security (e.g. by identifying harmful websites). Motivated by the lack of ready-to-use solutions, in this paper we present a flexible and accessible toolkit for structure and content mining, able to crawl, download, extract and index resources from the Web. While being easily configurable to work in the "surface" Web, our suite is specifically tailored to explore the Tor dark Web, i.e. the ensemble of Web servers composing the world's most famous darknet. Notably, the toolkit is not just a Web scraper, but it includes two mining modules, respectively able to prepare content to be fed to an (external) semantic engine, and to reconstruct the graph structure of the explored portion of the Web. Other than discussing in detail the design, features and performance of our toolkit, we report the findings of a preliminary run over Tor, that clarify the potential of our solution.

Phosphoinositides (PtdIns) control fundamental cell processes, and inherited defects of PtdIns kinases or phosphatases cause severe human diseases, including Lowe syndrome due to mutations in OCRL, which encodes a PtdIns(4,5)P2 5-phosphatase. Here we unveil a lysosomal response to the arrival of autophagosomal cargo in which OCRL plays a key part. We identify mitochondrial DNA and TLR9 as the cargo and the receptor that triggers and mediates, respectively, this response. This lysosome-cargo response is required to sustain the autophagic flux and involves a local increase in PtdIns(4,5)P2 that is confined in space and time by OCRL. Depleting or inhibiting OCRL leads to an accumulation of lysosomal PtdIns(4,5)P2, an inhibitor of the calcium channel mucolipin-1 that controls autophagosome-lysosome fusion. Hence, autophagosomes accumulate in OCRL-depleted cells and in the kidneys of Lowe syndrome patients. Importantly, boosting the activity of mucolipin-1 with selective agonists restores the autophagic flux in cells from Lowe syndrome patients.

MicroRNAs play a fundamental role in retinal development and function. To characterise the miRNome of the human retina, we carried out deep sequencing analysis on sixteen individuals. We established the catalogue of retina-expressed miRNAs, determined their relative abundance and found that a small number of miRNAs accounts for almost 90% of the retina miRNome. We discovered more than 3000 miRNA variants (isomiRs), encompassing a wide range of sequence variations, which include seed modifications that are predicted to have an impact on miRNA action. We demonstrated that a seed-modifying isomiR of the retina-enriched miR-124-3p was endowed with different targeting properties with respect to the corresponding canonical form. Moreover, we identified 51 putative novel, retina-specific miRNAs and experimentally validated the expression for nine of them. Finally, a parallel analysis of the human Retinal Pigment Epithelium (RPE)/choroid, two tissues that are known to be crucial for retina homeostasis, yielded notably distinct miRNA enrichment patterns compared to the retina. The generated data are accessible through an ad hoc database. This study is the first to reveal the complexity of the human retina miRNome at nucleotide resolution and constitutes a unique resource to assess the contribution of miRNAs to the pathophysiology of the human retina.

The archaeological discoveries of recent years and the latest studies about the uses and customs of Italic aristocracies of the Apulian-Lucanian area have added some relevant data concerning to the class of personal adornments and symbolic objects, fundamental elements underpinning the phenomenon of the birth of aristocracies between the eighth and seventh century BC. Even more indicative, as confirmed by the latest research and depth analysis of some archaeological finds, is the bond that unites these indigenous aristocracies to those of the Tyrrhenian area, active since the ninth century BC. Testimony of such deep relationships are the ornaments found in extraordinary burials, some of which they add, to the preciousness of the material, the sophistication of the workmanship and the rare and exotic character (amber, ivory and faïence). Consider, for example, the sumptuous parures characterizing burials of Enotrian and North-Lucanian princesses (Alianello, Chiaromonte, Baragiano and Braida di Vaglio), characterized by countless amber beads, some of which depict animals whose origin sinks into religious beliefs related to earliest times and perhaps coming from foreign cultural environments, from ivory and bronze beads, as well as scarabs and faïence figurines of Egyptian deities. The parures found in the tombs of Daunian princesses are no less interesting, though less sumptuous, which are marked not only by several personal adornments but also by the presence of symbolic objects in precious metals, many of which imported by Southern Etruria (diadems, sceptres, distaffs) that emphasize royal status of the deceased with a definite reminder of the aristocracies sung by Homer in his poems. The interest and the reference to the Homeric poems are even higher at the presence of the unusual ritual of horses burial matched to the tombs of Daunian princesses. A key role is undoubtedly played by archaic figured ambers, powerful amulets able to defeat the evil eye and the fear of death, whose subjects evoke mythical figures and characters related to funerary and Dionysian world, whose task was to accompany and protect the dead during their long journey into the darkness of Underworld toward the 'everlasting salvation.'

The study takes up some issues relating to the location of the workshops that produced the valuable figured ambers that marked the aristocratic burials of southern Italy from the eighth to fifth century BC. The contribution of findings and recent studies enabled us to assign some groups of artifacts to the activity of different workshops and even to identify outstanding artistic personalities, highlighting the undeniable stylistic connections between them.

We present hybrid lattice Boltzmann simulations of extensile and contractile active fluids where we incorporate phenomenologically the tendency of active particles such as cell and bacteria, to move, or swim, along the local orientation. Quite surprisingly, we show that the interplay between alignment and activity can lead to completely different results, according to geometry (periodic boundary conditions or confinement between flat walls) and nature of the activity (extensile or contractile). An interesting generic outcome is that the alignment interaction can transform stationary active patterns into continuously moving ones: the dynamics of these evolving patterns can be oscillatory or chaotic according to the strength of the alignment term. Our results suggest that flow-polarisation alignment can have important consequences on the collective dynamics of active fluids and active gel.

Here we study theoretically the dynamics of a 2D and a 3D isotropic droplet in a nematic liquid crystal under a shear flow. We find a large repertoire of possible nonequilibrium steady states as a function of the shear rate and of the anchoring of the nematic director field at the droplet surface. We first discuss homeotropic anchoring. For weak anchoring, we recover the typical behaviour of a sheared isotropic droplet in a binary fluid, which rotates, stretches and can be broken by the applied flow. For intermediate anchoring, new possibilities arise due to elastic effects in the nematic fluid. We find that in this regime the 2D droplet can tilt and move in the flow, or tumble incessantly at the centre of the channel. For sufficiently strong anchoring, finally, one or both of the topological defects which form close to the surface of the isotropic droplet in equilibrium detach from it and get dragged deep into the nematic state by the flow. In 3D, instead, the Saturn ring associated with the normal anchoring disclination line can be deformed and shifted downstream by the flow, but remains always localized in the proximity of the droplet, at least for the parameter range we explored. Tangential anchoring in 2D leads to a different dynamic response, as the boojum defects characteristic of this situation can unbind from the droplet under a weaker shear with respect to the normal anchoring case. Our results should stimulate further experiments with inverted liquid crystal emulsions under shear, as most of the predictions can be testable in principle by monitoring the evolution of liquid crystalline orientation patterns or by tracking the position and shape of the droplet over time.

Bioventing is a technology used to abate the presence of pollutants in the subsoil. Microorganisms biodegrade the pollutant but the biochemical reaction requires oxygen and so an airflow is induced in the subsoil by means of injection and/or extraction wells. Costs, final result and decontamination time are reliant on contaminant type, soil permeability and several other factors, but oxygen subsoil concentration plays a very important role. For this reason a rational choice of well locations and flow rates is required. The mathematical definition of the optimal design problem will be set-up starting from a simplified mathematical model describing the bioventing system. A formal definition of decontaminated subsoil will be given and the set of system control variables will be identified. Optimization strategies such as cost minimization and time optimization will be mathematically described.

The effects of a nonminimally coupled curvature-matter model of gravity on planetary orbits are computed. The parameters of the model are then constrained by the observation of Mercury orbit.

In this paper, we propose a viable encoding scheme that, to the best of our knowledge, is the first one to guarantee both perfect secrecy (i.e., no information leakage) and reliable communication over the generalized Ozarow-Wyner's wire-tap channel. To this end, we first introduce a metric called uncertainty rate that, similarly to the equivocation rate metric, captures the amount of information leaked by a coding scheme in the considered threat model, but it is simpler to apply in the context of linear codes. Based on this metric, we provide an alternative and simpler proof of the known result that no linear error correcting code alone can achieve perfect secrecy. Finally, we propose a constructive solution combining secret sharing and linear error-correcting codes, and we show that our solution provides the desired combination of reliable and perfectly secret communication. The provided solution, other than being supported by thorough analysis, is viable in practical communication systems. (C) 2016 Elsevier B.V. All rights reserved. In a typical secure communication system, messages undergo two different encodings: an error-correcting code is applied at the physical layer to ensure correct reception by the addressee (integrity), while at an upper protocol layer cryptography is leveraged to enforce secrecy with respect to eavesdroppers (confidentiality). All constructive solutions proposed so far to concurrently achieve both integrity and confidentiality at the physical layer, aim at meeting the secrecy capacity of the channel, i.e., at maximizing the rate of the code while guaranteeing an asymptotically small information leakage.

We consider a scenario in which certain target locations are monitored through sensors, which are scattered all over a considered area. A quality-of-service threshold imposes that, at any given time, a predefined percentage of the overall number of targets must be monitored. Furthermore, the activated sensors must be able to transmit the sensed information to a central base station, and the different roles assumed by the sensors (sensing, relay or idle) lead to different energy consumptions. We propose an exact algorithm to solve the problem of maximizing the operational time in this scenario, and test it on a set of benchmark instances.