Integrating ontologies into the collaborative authoring of learning objects

Authoring learning material is a multi-disciplinary undertaking where different people can play their role. Any support that can be provided for the collaboration of instructional designers, pedagogues, media designers, and students, among others, is welcome. In particular, metadata annotation of learning objects is an important task within the whole authoring process. This work presents the first resulting products and approaches from the MD2 project, consisting of a service-oriented framework and a tool to support the integrated, ontology-based collaborative annotation of learning objects

Abnormal morphology biases haematocrit distribution in tumour vasculature and contributes to heterogeneity in tissue oxygenation

Oxygen heterogeneity in solid tumors is recognized as a limiting factor for therapeutic efficacy. This heterogeneity arises from the abnormal vascular structure of the tumor, but the precise mechanisms linking abnormal structure and compromised oxygen transport are only partially understood. In this paper, we investigate the role that red blood cell (RBC) transport plays in establishing oxygen heterogeneity in tumor tissue. We focus on heterogeneity driven by network effects, which are challenging to observe experimentally due to the reduced fields of view typically considered. Motivated by our findings of abnormal vascular patterns linked to deviations from current RBC transport theory, we calculated average vessel lengths L⎯⎯ and diameters d⎯⎯ from tumor allografts of three cancer cell lines and observed a substantial reduction in the ratio λ=L⎯⎯/d⎯⎯ compared to physiological conditions. Mathematical modeling reveals that small values of the ratio λ (i.e., λ<6 ) can bias hematocrit distribution in tumor vascular networks and drive heterogeneous oxygenation of tumor tissue. Finally, we show an increase in the value of λ in tumor vascular networks following treatment with the antiangiogenic cancer agent DC101. Based on our findings, we propose λ as an effective way of monitoring the efficacy of antiangiogenic agents and as a proxy measure of perfusion and oxygenation in tumor tissue undergoing antiangiogenic treatment

Validation of a Novel, Sensitive, and Specific Urine-Based Test for Recurrence Surveillance of Patients With Non-Muscle-Invasive Bladder Cancer in a Comprehensive Multicenter Study

Bladder cancer (BC), the most frequent malignancy of the urinary system, is ranked the sixth most prevalent cancer worldwide. Of all newly diagnosed patients with BC, 70–75% will present disease confined to the mucosa or submucosa, the non-muscle-invasive BC (NMIBC) subtype. Of those, approximately 70% will recur after transurethral resection (TUR). Due to high rate of recurrence, patients are submitted to an intensive follow-up program maintained throughout many years, or even throughout life, resulting in an expensive follow-up, with cystoscopy being the most cost-effective procedure for NMIBC screening. Currently, the gold standard procedure for detection and follow-up of NMIBC is based on the association of cystoscopy and urine cytology. As cystoscopy is a very invasive approach, over the years, many different noninvasive assays (both based in serum and urine samples) have been developed in order to search genetic and protein alterations related to the development, progression, and recurrence of BC. TERT promoter mutations and FGFR3 hotspot mutations are the most frequent somatic alterations in BC and constitute the most reliable biomarkers for BC. Based on these, we developed an ultra-sensitive, urine-based assay called Uromonitor®, capable of detecting trace amounts of TERT promoter (c.1-124C > T and c.1-146C > T) and FGFR3 (p.R248C and p.S249C) hotspot mutations, in tumor cells exfoliated to urine samples. Cells present in urine were concentrated by the filtration of urine through filters where tumor cells are trapped and stored until analysis, presenting long-term stability. Detection of the alterations was achieved through a custom-made, robust, and highly sensitive multiplex competitive allele-specific discrimination PCR allowing clear interpretation of results. In this study, we validate a test for NMIBC recurrence detection, using for technical validation a total of 331 urine samples and 41 formalin-fixed paraffin-embedded tissues of the primary tumor and recurrence lesions from a large cluster of urology centers. In the clinical validation, we used 185 samples to assess sensitivity/specificity in the detection of NMIBC recurrence vs. cystoscopy/cytology and in a smaller cohort its potential as a primary diagnostic tool for NMIBC. Our results show this test to be highly sensitive (73.5%) and specific (93.2%) in detecting recurrence of BC in patients under surveillance of NMIBC.This study was supported by FCT (“Portuguese Foundation for Science and Technology”) through a PhD grant to RB (SFRH/ BD/111321/2015). Further funding was obtained from the project “Advancing cancer research: from basic knowledge to application” NORTE-01-0145-FEDER-000029: “Projetos Estruturados de I & D & I,” funded by Norte 2020—Programa Operacional Regional do Norte. This article is a result of the project PTDC/MED-ONC/31438/2017 (The Other Faces of Telomerase: Looking beyond Tumor Immortalization), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI) and by Portuguese funds through FCT. Further funding by the European Regional Development Fund (ERDF) through the Operational Programme for Competitiveness and Internationalisation— COMPETE 2020, and Portuguese national funds via FCT, under project POCI-01-0145-FEDER-016390:CANCEL STEM

Understanding the enhanced synchronization of delay-coupled networks with fluctuating topology

We study the dynamics of networks with coupling delay, from which the connectivity changes over time. The synchronization properties are shown to depend on the interplay of three time scales: the internal time scale of the dynamics, the coupling delay along the network links and time scale at which the topology changes. Concentrating on a linearized model, we develop an analytical theory for the stability of a synchronized solution. In two limit cases the system can be reduced to an “effective” topology: In the fast switching approximation, when the network fluctuations are much faster than the internal time scale and the coupling delay, the effective network topology is the arithmetic mean over the different topologies. In the slow network limit, when the network fluctuation time scale is equal to the coupling delay, the effective adjacency matrix is the geometric mean over the adjacency matrices of the different topologies. In the intermediate regime the system shows a sensitive dependence on the ratio of time scales, and specific topologies, reproduced as well by numerical simulations. Our results are shown to describe the synchronization properties of fluctuating networks of delay-coupled chaotic maps

Phonon hydrodynamics in frequency-domain thermoreflectance experiments

The hydrodynamic heat transport equation with appropriate boundary conditions and ab-initio calculated coefficients is validated by comparing the corresponding analytical and numerical solutions with frequency domain thermoreflectance experimental measurements in silicon. Special attention is devoted to identifying the resistive effects appearing at the interface between the metal transducer and the silicon substrate. We find that a Fourier model using a frequency-dependent effective thermal conductivity cannot simultaneously explain the experimental phase shifts and the amplitude of the temperature oscillations, whereas the hydrodynamic model using intrinsic parameters provides good agreement across a wide temperature range. In addition, new phenomenology appearing at reduced length and time scales in this kind of experiment at different temperatures is shown. Specifically, we find hydrodynamic modes of thermal transport that are analogous to pressure- and shear-wave propagation in viscoelastic media

Phonon hydrodynamics in frequency-domain thermoreflectance experiments

The hydrodynamic heat transport equation with appropriate boundary conditions and ab-initio calculated coefficients is validated by comparing the corresponding analytical and numerical solutions with frequency domain thermoreflectance experimental measurements in silicon. Special attention is devoted to identifying the resistive effects appearing at the interface between the metal transducer and the silicon substrate. We find that a Fourier model using a frequency-dependent effective thermal conductivity cannot simultaneously explain the experimental phase shifts and the amplitude of the temperature oscillations, whereas the hydrodynamic model using intrinsic parameters provides good agreement across a wide temperature range. In addition, new phenomenology appearing at reduced length and time scales in this kind of experiment at different temperatures is shown. Specifically, we find hydrodynamic modes of thermal transport that are analogous to pressure- and shear-wave propagation in viscoelastic media

Phonon hydrodynamics in frequency-domain thermoreflectance experiments

The hydrodynamic heat transport equation with appropriate boundary conditions and ab initio calculated coefficients is validated by comparing the corresponding analytical and numerical solutions with frequency-domain thermoreflectance experimental measurements in silicon. Special attention is devoted to identifying the resistive effects appearing at the interface between the metal transducer and the silicon substrate. We find that a Fourier model using frequency-dependent effective thermal conductivity cannot simultaneously explain the experimental phase shifts and the amplitude of the temperature oscillations, whereas the hydrodynamic model using intrinsic parameters provides good agreement across a wide temperature range. In addition, phenomenology appearing at reduced length and time scales in this kind of experiment at different temperatures is shown. Specifically, we find hydrodynamic modes of thermal transport that are analogous to pressure- A nd shear-wave propagation in viscoelastic media. © 2020 American Physical Society

Observation of second sound in a rapidly varying temperature field in Ge

Second sound is known as the thermal transport regime where heat is carried by temperature waves. Its experimental observation was previously restricted to a small number of materials, usually in rather narrow temperature windows. We show that it is possible to overcome these limitations by driving the system with a rapidly varying temperature field. High-frequency second sound is demonstrated in bulk natural Ge between 7 K and room temperature by studying the phase lag of the thermal response under a harmonic high-frequency external thermal excitation and addressing the relaxation time and the propagation velocity of the heat waves. These results provide a route to investigate the potential of wave-like heat transport in almost any material, opening opportunities to control heat through its oscillatory nature