Social networks help to infer causality in the tumor microenvironment.

BACKGROUND: Networks have become a popular way to conceptualize a system of interacting elements, such as electronic circuits, social communication, metabolism or gene regulation. Network inference, analysis, and modeling techniques have been developed in different areas of science and technology, such as computer science, mathematics, physics, and biology, with an active interdisciplinary exchange of concepts and approaches. However, some concepts seem to belong to a specific field without a clear transferability to other domains. At the same time, it is increasingly recognized that within some biological systems-such as the tumor microenvironment-where different types of resident and infiltrating cells interact to carry out their functions, the complexity of the system demands a theoretical framework, such as statistical inference, graph analysis and dynamical models, in order to asses and study the information derived from high-throughput experimental technologies. RESULTS: In this article we propose to adopt and adapt the concepts of influence and investment from the world of social network analysis to biological problems, and in particular to apply this approach to infer causality in the tumor microenvironment. We showed that constructing a bidirectional network of influence between cell and cell communication molecules allowed us to determine the direction of inferred regulations at the expression level and correctly recapitulate cause-effect relationships described in literature. CONCLUSIONS: This work constitutes an example of a transfer of knowledge and concepts from the world of social network analysis to biomedical research, in particular to infer network causality in biological networks. This causality elucidation is essential to model the homeostatic response of biological systems to internal and external factors, such as environmental conditions, pathogens or treatments

Origin of orbital ferromagnetism and giant magnetic anisotropy at the nanoscale

The origin of orbital magnetism recently observed in different nanostructured films and particles is discussed as a consequence of spin-orbit coupling. It is shown that contact potentials induced at the thin film surface by broken symmetries, as domain boundaries in self-assembled monolayers, lead to orbital states that in some cases are of large radius. The component of the angular momentum normal to the surface can reach very high values that decrease the total energy by decreasing spin-orbit interaction energy. Intraorbital ferromagnetic spin correlations induce orbital momenta alignment. The estimated values of the magnetic moments per atom are in good agreement with the experimental observations in thiol capped gold films and nanoparticles

Applications of CVD to Produce Thin Films for Solid‐State Devices

Thin films of Pt‐YSZ and Pd‐ZrO2 cermets by chemical vapor deposition (CVD) from metallorganic precursors (MOCVD) were evaluated as electrode in solid‐state devices. Morphology and structural characteristics were studied by X‐ray diffraction (XRD), scanning electronic microscopy, atomic force microscopy (AFM), and transmission electronic microscopy (TEM). Electrochemical performance was determined using Tafel and electrochemical impedance spectroscopy methods. Metallorganic precursors were used (metal‐acetylacetonates), and argon and oxygen were used as the carrier and reactive gases, respectively. The particle average size was less than 20 nm, with high and uniform particle dispersion according to TEM measurements

Identifying biological mechanisms for favorable cancer prognosis using non-hypothesis-driven iterative survival analysis.

Survival analyses based on the Kaplan-Meier estimate have been pervasively used to support or validate the relevance of biological mechanisms in cancer research. Recently, with the appearance of gene expression high-throughput technologies, this kind of analysis has been applied to tumor transcriptomics data. In a 'bottom-up' approach, gene-expression profiles that are associated with a deregulated pathway hypothetically involved in cancer progression are first identified and then subsequently correlated with a survival effect, which statistically supports or requires the rejection of such a hypothesis. In this work, we propose a 'top-down' approach, in which the clinical outcome (survival) is the starting point that guides the identification of deregulated biological mechanisms in cancer by a non-hypothesis-driven iterative survival analysis. We show that the application of our novel method to a population of ~2,000 breast cancer patients of the METABRIC consortium allows the identification of several well-known cancer mechanisms, such as ERBB4, HNF3A and TGFB pathways, and the investigation of their paradoxical dual effect. In addition, several novel biological mechanisms are proposed as potentially involved in cancer progression. The proposed exploratory methodology can be considered both alternative and complementary to classical 'bottom-up' approaches for validation of biological hypotheses. We propose that our method may be used to better characterize cancer, and may therefore impact the future design of therapies that are truly molecularly tailored to individual patients. The method, named SURCOMED, was implemented as a web-based tool, which is publicly available at http://surcomed.vital-it.ch. R scripts are also available at http://surcomed.sourceforge.net)

Relaciones entre el conocimiento cotidiano y el conocimiento científico: comprendiendo cómo cambia la materia

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Hipparion dispersal in Europe: magnetostratigraphic constraints from the Daroca area (Spain)

The Nombrevilla section in the Calatayud-Daroca basin (Central Spain) bears one of the best late Aragonian to early Vallesian large and small vertebrate fossil records in Europe, including important findings of the equid Hipparion. Magnetostratigraphic dating of the Nombrevilla section thus provides further age constraints on the timing of Hipparion dispersal in Europe, a bioevent which defines the base of the Vallesian mammal stage. Correlation of the Nombrevilla magnetic polarity stratigraphy to the geomagnetic polarity time scale is supported by the identification of the characteristic long normal chron C5n in the upper half of the section,... (Ver más) in association with early Vallesian (early late Miocene) fossils. The classic mammal fossil site Nombrevilla 1, recording the earliest occurrence of Hipparion, correlates to the lower third of chron C5n, and yields an interpolated age of about 10.7-10.8 Ma. This age is in agreement with magnetostratigraphic dating of earliest occurrences in Siwaliks of Pakistan and some 40Ar/39Ar ages of Mediterranean sites. The youngest pre-Hipparion large mammal fossil record corresponds to Nombrevilla 9, a site wich approximately correlates to chron C5r.1n, at about 11.1 Ma. This result is nearly in conflict with the data from the Vallès-Penedès, where a Hipparion bearing site is correlated to the same chron. In addition, Nombrevilla 9 yields a small mammal assemblage which corresponds to local zone H, a biozone wich was classically correlated to the lower Vallesian. This implies a diachrony of about 300 kyr between the lower boundary of zone H and the first occurrence of Hipparion (base of the Vallesian) in the Calatayud-Daroca basin. Correlation of the Aragonian levels of Nombrevilla 2, 3 and 4 is not yet certain and would require further downward extension of the magnetostratigraphy in a neighbouring section. Nevertheless, we can confidently say these localities are younger than 11.6 Ma

Ataxia and focal dystonia in Kallmann syndrome

A case of Kallmann syndrome (KS) associated with rare neurological manifestations is presented. Cerebellar ataxia probably caused by a small posterior fossa and a focal dystonia affecting the left lower limb expand the spectrum of neurological manifestations occurring in KS. Further studies are needed to better understand these manifestations