3,415 research outputs found
Active Depth Estimation: Stability Analysis and its Applications
Recovering the 3D structure of the surrounding environment is an essential
task in any vision-controlled Structure-from-Motion (SfM) scheme. This paper
focuses on the theoretical properties of the SfM, known as the incremental
active depth estimation. The term incremental stands for estimating the 3D
structure of the scene over a chronological sequence of image frames. Active
means that the camera actuation is such that it improves estimation
performance. Starting from a known depth estimation filter, this paper presents
the stability analysis of the filter in terms of the control inputs of the
camera. By analyzing the convergence of the estimator using the Lyapunov
theory, we relax the constraints on the projection of the 3D point in the image
plane when compared to previous results. Nonetheless, our method is capable of
dealing with the cameras' limited field-of-view constraints. The main results
are validated through experiments with simulated data.Comment: 7 pages, 3 figures, conferenc
Counteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles
FCT/MCTES - UID/Multi/04378/2019. FCT/MCTES - SFRH/BPD/124612/2016.Purpose: Progression of chronic myeloid leukemia (CML) is frequently associated with increased angiogenesis at the bone marrow mediated by exosomes. The capability of gold nanoparticles (AuNPs) functionalized with antiangiogenic peptides to hinder the formation of new blood vessels has been demonstrated in a chorioallantoic membrane (CAM) model. Methods: Exosomes of K562 CML cell line were isolated and their angiogenic effect assessed in a CAM model. AuNPs functionalized with antiangiogenic peptides were used to block the angiogenic effect of CML-derived exosomes, assessed by evaluation of expression levels of key modulators involved in angiogenic pathways - VEGFA, VEGFR1 (also known as FLT1) and IL8. Results: Exosomes isolated from K562 cells promoted the doubling of newly formed vessels associated with the increase of VEGFR1 expression. This is a concentration and timedependent effect. The AuNPs functionalized with antiangiogenic peptides were capable to block the angiogenic effect by modulating VEGFR1 associated pathway. Conclusion: Exosomes derived from blast cells are capable to trigger (neo)-angiogenesis, a key factor for the progression and spreading of cancer, in particular in CML. AuNPs functionalized with specific antiangiogenic peptides are capable to block the effect of the exosomes produced by malignant cells via modulation of the intrinsic VEGFR pathway. Together, these data highlight the potential of nanomedicine-based strategies against cancer proliferation.publishersversionpublishe
Exploring RAB11A Pathway to Hinder Chronic Myeloid Leukemia-Induced Angiogenesis In Vivo
project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB.
This work is also funded by Fundação para a Ciência e Tecnologia in the scope of the project 2022.04315.PTDC.
Publisher Copyright:
© 2023 by the authors.Neoangiogenesis is generally correlated with poor prognosis, due to the promotion of cancer cell growth, invasion and metastasis. The progression of chronic myeloid leukemia (CML) is frequently associated with an increased vascular density in bone marrow. From a molecular point of view, the small GTP-binding protein Rab11a, involved in the endosomal slow recycling pathway, has been shown to play a crucial role for the neoangiogenic process at the bone marrow of CML patients, by controlling the secretion of exosomes by CML cells, and by regulating the recycling of vascular endothelial factor receptors. The angiogenic potential of exosomes secreted by the CML cell line K562 has been previously observed using the chorioallantoic membrane (CAM) model. Herein, gold nanoparticles (AuNPs) were functionalized with an anti-RAB11A oligonucleotide (AuNP@RAB11A) to downregulate RAB11A mRNA in K562 cell line which showed a 40% silencing of the mRNA after 6 h and 14% silencing of the protein after 12 h. Then, using the in vivo CAM model, these exosomes secreted by AuNP@RAB11A incubated K562 did not present the angiogenic potential of those secreted from untreated K562 cells. These results demonstrate the relevance of Rab11 for the neoangiogenesis mediated by tumor exosomes, whose deleterious effect may be counteracted via targeted silencing of these crucial genes; thus, decreasing the number of pro-tumoral exosomes at the tumor microenvironment.publishersversionpublishe
Nanotheranostics Targeting the Tumor Microenvironment
UID/Multi/04378/2019 SFRH/BPD/124612/2016 PD/BD/105734/2014Cancer is considered the most aggressive malignancy to humans, and definitely the major cause of death worldwide. Despite the different and heterogenous presentation of the disease, there are pivotal cell elements involved in proliferation, differentiation, and immortalization, and ultimately the capability to evade treatment strategies. This is of utmost relevance when we are just beginning to grasp the complexity of the tumor environment and the molecular "evolution" within. The tumor micro-environment (TME) is thought to provide for differentiation niches for clonal development that results in tremendous cancer heterogeneity. To date, conventional cancer therapeutic strategies against cancer are failing to tackle the intricate interplay of actors within the TME. Nanomedicine has been proposing innovative strategies to tackle this TME and the cancer cells that simultaneously provide for biodistribution and/or assessment of action. These nanotheranostics systems are usually multi-functional nanosystems capable to carry and deliver active cargo to the site of interest and provide diagnostics capability, enabling early detection, and destruction of cancer cells in a more selective way. Some of the most promising multifunctional nanosystems are based on gold nanoparticles, whose physic-chemical properties have prompt for the development of multifunctional, responsive nanomedicines suitable for combinatory therapy and theranostics. Herein, we shall focus on the recent developments relying on the properties of gold nanoparticles as the basis for nanotheranostics systems against the heterogeneity within the TME.publishersversionpublishe
Summer aggregations of the common eagle ray, Myliobatis aquila
The aggregation of multiple individuals is a long known behaviour in a variety of elasmobranchs, including reef sharks (Speed et al. 2011), hammerhead sharks (Klimley & Nelson 1984), whale sharks (Hoffmayer et al. 2007), devilrays (Ward-Page et al. 2013; Sobral & Afonso 2014), stingrays (Semeniuk & Rotley 2008), eagle rays (Silliman & Gruber 1999) and cownose rays (Smith et al. 1987). Various functions have been hypothesised to explain these aggregations, including feeding (e.g. Wilson et al. 2001; Rohner et al. 2013), courtship or mating (Whitney et al. 2004; Dudgeon et al. 2008), and cleaning stations (Dewar et al. 2008). However, apart from the obvious cases whenever individuals directly engage in reproductive activities, the social functions that these aggregations might serve are not understood or even described.
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Hyperthermia induced by gold nanoparticles and visible light photothermy combined with chemotherapy to tackle doxorubicin sensitive and resistant colorectal tumor 3D spheroids
UIDB/04378/2020 SFRH/BPD/124612/2016Current cancer therapies are frequently ineffective and associated with severe side effects and with acquired cancer drug resistance. The development of effective therapies has been hampered by poor correlations between pre-clinical and clinical outcomes. Cancer cell-derived spheroids are three-dimensional (3D) structures that mimic layers of tumors in terms of oxygen and nutrient and drug resistance gradients. Gold nanoparticles (AuNP) are promising therapeutic agents which permit diminishing the emergence of secondary effects and increase therapeutic efficacy. In this work, 3D spheroids of Doxorubicin (Dox)-sensitive and -resistant colorectal carcinoma cell lines (HCT116 and HCT116-DoxR, respectively) were used to infer the potential of the combination of chemotherapy and Au-nanoparticle photothermy in the visible (green laser of 532 nm) to tackle drug resistance in cancer cells. Cell viability analysis of 3D tumor spheroids suggested that AuNPs induce cell death in the deeper layers of spheroids, further potentiated by laser irradiation. The penetration of Dox and earlier spheroid disaggregation is potentiated in combinatorial therapy with Dox, AuNP functionalized with polyethylene glycol (AuNP@PEG) and irradiation. The time point of Dox administration and irradiation showed to be important for spheroids destabilization. In HCT116-sensitive spheroids, pre-irradiation induced earlier disintegration of the 3D structure, while in HCT116 Dox-resistant spheroids, the loss of spheroid stability occurred almost instantly in post-irradiated spheroids, even with lower Dox concentrations. These results point towards the application of new strategies for cancer therapeutics, reducing side effects and resistance acquisition.publishersversionpublishe
Liquid biopsies in myeloid malignancies
Funding Information: This work was supported by the Applied Molecular Biosciences Unit-UCIBIO which is financed by national funds from FCT/MCTES (UID/Multi/04378/2019).Hematologic malignancies are the most common type of cancer affecting children and young adults, and encompass diseases, such as leukemia, lymphoma, and myeloma, all of which impact blood associated tissues such as the bone marrow, lymphatic system, and blood cells. Clinical diagnostics of these malignancies relies heavily on the use of bone marrow samples, which is painful, debilitating, and not free from risks for leukemia patients. Liquid biopsies are based on minimally invasive assessment of markers in the blood (and other fluids) and have the potential to improve the efficacy of diagnostic/therapeutic strategies in leukemia patients, providing a useful tool for the real time molecular profiling of patients. The most promising noninvasive biomarkers are circulating tumor cells, circulating tumor DNA, microRNAs, and exosomes. Herein, we discuss the role of assessing these circulating biomarkers for the understanding of tumor progression and metastasis, tumor progression dynamics through treatment and for follow-up.publishersversionpublishe
Gene Therapy in Cancer Treatment: Why Go Nano?
The proposal of gene therapy to tackle cancer development has been instrumental for the
development of novel approaches and strategies to fight this disease, but the efficacy of the proposed
strategies has still fallen short of delivering the full potential of gene therapy in the clinic. Despite the
plethora of gene modulation approaches, e.g., gene silencing, antisense therapy, RNA interference,
gene and genome editing, finding a way to efficiently deliver these effectors to the desired cell and
tissue has been a challenge. Nanomedicine has put forward several innovative platforms to overcome
this obstacle. Most of these platforms rely on the application of nanoscale structures, with particular
focus on nanoparticles. Herein, we review the current trends on the use of nanoparticles designed for
cancer gene therapy, including inorganic, organic, or biological (e.g., exosomes) variants, in clinical
development and their progress towards clinical applications.This work was supported by the Applied Molecular Biosciences Unit - UCIBIO which is financed by
national funds from FCT (UIDB/04378/2020), CRR (SFRH/BPD/124612/2016) and LRG (Inn-Indigo 00002/2015 RA
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Assessing the compressive and impact behavior of plastic safety toe caps through computational modelling
Toe caps are one of the most important components in safety footwear, but have a significant contribution to the weight of the shoe. Efforts have been made to replace steel toe caps by polymeric ones, since they are lighter, insulated and insensitive to magnetic fields. Nevertheless, polymeric solutions require larger volumes, which has a negative impact on the shoe’s aesthetics. Therefore, safety footwear manufacturers are pursuing the development of an easy, low-cost and reliable solution to optimize this component. In this work, a solid mechanics toolbox built in the open-source computational library, OpenFOAM®, was used to simulate two laboratory standard tests (15 kN compression and 200 J impact tests). To model the polymeric material behavior, a neo-Hookean hyper-elasto-plastic material law with J2 plastic criteria was employed. A commercially available plastic toe cap was characterized, and the collected data was used for assessment purposes. Close agreements, between experimental and simulated values, were achieved for both tests, with an approximate error of 5.4% and 6.8% for the displacement value in compression and impact test simulations, respectively. The results clearly demonstrate that the employed open-source finite volume computational models offer reliable results and can support the design of toe caps for the R&D footwear industry.This work was funded by FEDER funds through the COMPETE 2020 Programme and National Funds through FCT-Portuguese Foundation for Science and Technology under the projects UIDB/05256/2020; UIDP/05256/2020 and FAMEST-Footwear, Advanced Materials, Equipment’s and Software Technologies (POCI-01-0247-FEDER-024529)
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