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Paulo Aguiar

Publications and source records attributed to Paulo Aguiar.

8 recordsLinked to original sources

HEROHE Challenge: assessing HER2 status in breast cancer without immunohistochemistry or in situ hybridization

Breast cancer is the most common malignancy in women, being responsible for more than half a million deaths every year. As such, early and accurate diagnosis is of paramount importance. Human expertise is required to diagnose and correctly classify breast cancer and define appropriate therapy, which depends on the evaluation of the expression of different biomarkers such as the transmembrane protein receptor HER2. This evaluation requires several steps, including special techniques such as immunohistochemistry or in situ hybridization to assess HER2 status. With the goal of reducing the number of steps and human bias in diagnosis, the HEROHE Challenge was organized, as a parallel event of the 16th European Congress on Digital Pathology, aiming to automate the assessment of the HER2 status based only on hematoxylin and eosin stained tissue sample of invasive breast cancer. Methods to assess HER2 status were presented by 21 teams worldwide and the results achieved by some of the proposed methods open potential perspectives to advance the state-of-the-art.

q-bio.QM

BACH: Grand Challenge on Breast Cancer Histology Images

Breast cancer is the most common invasive cancer in women, affecting more than 10% of women worldwide. Microscopic analysis of a biopsy remains one of the most important methods to diagnose the type of breast cancer. This requires specialized analysis by pathologists, in a task that i) is highly time- and cost-consuming and ii) often leads to nonconsensual results. The relevance and potential of automatic classification algorithms using hematoxylin-eosin stained histopathological images has already been demonstrated, but the reported results are still sub-optimal for clinical use. With the goal of advancing the state-of-the-art in automatic classification, the Grand Challenge on BreAst Cancer Histology images (BACH) was organized in conjunction with the 15th International Conference on Image Analysis and Recognition (ICIAR 2018). A large annotated dataset, composed of both microscopy and whole-slide images, was specifically compiled and made publicly available for the BACH challenge. Following a positive response from the scientific community, a total of 64 submissions, out of 677 registrations, effectively entered the competition. From the submitted algorithms it was possible to push forward the state-of-the-art in terms of accuracy (87%) in automatic classification of breast cancer with histopathological images. Convolutional neuronal networks were the most successful methodology in the BACH challenge. Detailed analysis of the collective results allowed the identification of remaining challenges in the field and recommendations for future developments. The BACH dataset remains publically available as to promote further improvements to the field of automatic classification in digital pathology.

cs.CV

μSpikeHunter: An advanced computational tool for the analysis of neuronal communication and action potential propagation in microfluidic platforms

Understanding neuronal communication is fundamental in neuroscience but there are few methodologies offering detailed analysis for well-controlled conditions. By interfacing microElectrode arrays with microFluidics (μEF devices), it is possible to compartmentalize neuronal cultures with a specified alignment of axons and microelectrodes. This setup allows extracellular recordings of spike propagation with high signal-to-noise ratio over the course of several weeks. Addressing these μEF systems we developed an advanced, yet easy-to-use, open-source computational tool, μSpikeHunter, which provides detailed quantification of several communication-related properties such as propagation velocity, conduction failure, spike timings, and coding mechanisms. The combination of μEF devices and μSpikeHunter can be used in the context of standard neuronal cultures or with co-culture configurations where, for example, communication between sensory neurons and other cell types is monitored and assessed. The ability to analyze axonal signals (in a user-friendly, time-efficient, high-throughput manner) opens doors to new approaches to studies of peripheral innervation, neural coding, and neuroregeneration approaches, among many others. We demonstrate the use of μSpikeHunter in dorsal root ganglion neurons where we analyze the presence of anterograde signals in μEF devices.

q-bio.QM

Backward stochastic differential equation approach to modeling of gene expression

In this article, we introduce a novel backward method to model stochastic gene expression and protein level dynamics. The protein amount is regarded as a diffusion process and is described by a backward stochastic differential equation (BSDE). Unlike many other SDE techniques proposed in the literature, the BSDE method is backward in time; that is, instead of initial conditions it requires the specification of endpoint ("final") conditions, in addition to the model parametrization. To validate our approach we employ Gillespie's stochastic simulation algorithm (SSA) to generate (forward) benchmark data, according to predefined gene network models. Numerical simulations show that the BSDE method is able to correctly infer the protein level distributions that preceded a known final condition, obtained originally from the forward SSA. This makes the BSDE method a powerful systems biology tool for time reversed simulations, allowing, for example, the assessment of the biological conditions (e.g. protein concentrations) that preceded an experimentally measured event of interest (e.g. mitosis, apoptosis, etc.).

physics.bio-ph

Sachs-Wolfe effect in some anisotropic models

In this work it is shown for some spatially homogeneous but anisotropic models how the inhomogeneities in the distribution of matter on the surface of the last scattering produce anisotropies in large angular scales (larger than $\vartheta \gtrsim 2^\circ$) which do not differ from the ones produced in Friedmann-Lemaître-Robertson-Walker (FLRW) geometries. That is, for these anisotropic models, the imprint left on the cosmic microwave background radiation (CMBR) by the primordial density fluctuations, in the form of a fractional variation of the temperature of this radiation, is governed by the same expression as the one given for FLRW models. More precisely, under adiabatic initial conditions, the classical Sachs-Wolfe effect is recovered, provided the anisotropy of the overall expansion is small. This conclusion is in agreement with previous work on the same anisotropic models where we found that they may go through an `isotropization' process up to the point that the observations are unable to distinguish them from the standard FLRW model, if the Hubble parameters along the orthogonal directions are assumed to be approximately equal at the present epoch. Here we assumed upper bounds on the present values of anisotropic parameters imposed by COBE observations.

astro-ph

Model for Osteosarcoma-9 as a Potent Factor in Cell Survivor and Resistance to Apoptosis

In this paper we use a simple toy model to explore the function of the gene Osteosarcoma-9. We are in particular interested in understanding the role of this gene as a potent anti-apoptotic factor. The theoretical description is constrained by experimental data from induction of apoptosis in cells where OS-9 is overexpressed. The data available suggest that OS-9 promotes cell viability and confers resistance to apoptosis, potentially implicating OS-9 in the survival of cancer cells. Three different apoptosis inducing mechanisms were tested and are here modelled. More complex and realistic models are also discussed.

q-bio.SC

Dust-filled axially symmetric universes with a cosmological constant

Following the recent recognition of a positive value for the vacuum energy density and the realization that a simple Kantowski-Sachs model might fit the classical tests of cosmology, we study the qualitative behavior of three anisotropic and homogeneous models: Kantowski-Sachs, Bianchi type-I and Bianchi type-III universes, with dust and a cosmological constant, in order to find out which are physically permitted. We find that these models undergo isotropization up to the point that the observations will not be able to distinguish between them and the standard model, except for the Kantowski-Sachs model $(Ω_{k_{0}}<0)$ and for the Bianchi type-III $(Ω_{k_{0}}>0)$ with $Ω_{Λ_{0}}$ smaller than some critical value $Ω_{Λ_{M}}$. Even if one imposes that the Universe should be nearly isotropic since the last scattering epoch ($z\approx 1000$), meaning that the Universe should have approximately the same Hubble parameter in all directions (considering the COBE 4-Year data), there is still a large range for the matter density parameter compatible with Kantowsky-Sachs and Bianchi type-III if $|Ω_0+Ω_{Λ_0}-1|\leq δ$, for a very small $δ$ . The Bianchi type-I model becomes exactly isotropic owing to our restrictions and we have $Ω_0+Ω_{Λ_0}=1$ in this case. Of course, all these models approach locally an exponential expanding state provided the cosmological constant $Ω_Λ>Ω_{Λ_{M}}$.

gr-qc

Axially Symmetric Cosmological Models with Perfect Fluid and Cosmological Constant

Following recent considerations of a non-zero value for the vacuum energy density and the realization that a simple Kantowski-Sachs model might fit the classical tests of cosmology, we study the qualitative behavior of three anisotropic and homogeneous models: Kantowski-Sachs, Bianchi I and Bianchi III universes, with dust and cosmological constant, in order to find out which are physically permitted. In fact, these models undergo isotropisation, except for the Kantowski-Sachs model (Omega_{k_{0}}>0) with Omega_{Lambda_{0}}< Omega_{Lambda_{M}} and for the Bianchi III (Omega_{k_{0}}<0) with Omega_{Lambda_{0}}<Omega_{Lambda_{M}}, and the observations will not be able to distinguish between these models and the standard model. If we impose that the Universe should be very much isotropic since the last scattering epoch (z approximately 1000), meaning that the Universe should have approximately the same Hubble parameter in all directions, we are led to a matter density parameter very close to the unity at the present time.

astro-ph