392 research outputs found

    Interference suppression with physical-layer network coding and MIMO for multi-way channels

    Get PDF
    Orthogonal techniques (such as TDMA – time division multiple access) are traditionally used when a set of terminals wants to exchange data and a relay is required when wireless terminals cannot communicate directly. This paper proposes two schemes to address multi-way channels when a set of terminals wants to exchange data. Both proposed schemes consist of a first phase based on virtual MIMO with lattice reduction-aided (LRA) detection at the relay, establishing a multiple access channel (MAC). Two new strategies are then proposed for the second (multicast) phase; one for single antenna terminals and another for multiple-input multiple-output (MIMO) terminals. The second strategy achieves interference suppression by successively combining physical layer network coding and MIMO detection (with LRA detectors also at the terminals). The paper assesses a 3 terminals network with a relay for which a TDMA-based scheme would require 6 time-slots, while the proposed strategy for MIMO terminals is able to exchange the information between all terminals using 2 time-slots only. This latter scheme is easily scalable to a higher number of terminals, and always able to accomplish the exchange of messages between all of them in just 2 time-slots, although limited by the number of antennas that the terminals can fit and also the MIMO processing complexity they can afford.info:eu-repo/semantics/acceptedVersio

    Mechanobiology of Colorectal Cancer

    Get PDF
    In this review, the mechanobiology of colorectal cancer (CRC) are discussed. Mecha-notransduction of CRC is addressed considering the relationship of several biophysical cues and biochemical pathways. Mechanobiology is focused on considering how it may influence epithelial cells in terms of motility, morphometric changes, intravasation, circulation, extravasation, and metastization in CRC development. The roles of the tumor microenvironment, ECM, and stroma are also discussed, taking into account the influence of alterations and surface modifications on mechanical properties and their impact on epithelial cells and CRC progression. The role of cancer-associated fibroblasts and the impact of flow shear stress is addressed in terms of how it affects CRC metastization. Finally, some insights concerning how the knowledge of biophysical mechanisms may contribute to the development of new therapeutic strategies and targeting molecules and how mechanical changes of the microenvironment play a role in CRC disease are presented.The authors are grateful to Ana Silva ([email protected]) for expert assistance with graphical design and to Portuguese Fundação para a Ciência e a Tecnologia (FCT) for funds in the framework of the project Instituto de Investigação e Inovação em Saúde (i3S), ref. ID/BIM/04293/2020

    Alternative regimens for prostate cancer treatment using radiation therapy

    Get PDF
    Purpose/Objective: The purpose of this work was to determine biologically equivalent alternative regimens for the treatment of prostate cancer using External Beam Radiotherapy (EBRT) and Low Dose-Rate Brachytherapy (LDRBT) with 125I implants and to evaluate the sensitivity of these regimens to different sets of radiobiological parameters of the Linear-Quadratic (LQ) model

    Neurohormonal modulation: The new paradigm of pharmacological treatment of heart failure

    Get PDF
    The current paradigm of medical therapy for heart failure with reduced ejection fraction (HFrEF) is triple neurohormonal blockade with an angiotensin-converting enzyme inhibitor (ACEI), a beta-blocker (BB) and a mineralocorticoid receptor antagonist (MRA). However, three-year mortality remains over 30%. Stimulation of counter-regulatory systems in addition to neurohormonal blockade constitutes a new paradigm, termed neurohormonal modulation. Sacubitril/valsartan is the first element of this new strategy. PARADIGM-HF was the largest randomized clinical trial conducted in HFrEF. It included 8442 patients and compared the efficacy and safety of sacubitril/valsartan versus enalapril. The primary endpoint was the composite of cardiovascular mortality and hospitalization due to HF, which occurred in 914 (21.8%) patients receiving sacubitril/valsartan and in 1117 (26.5%) patients receiving enalapril (HR 0.8, 95% CI 0.73-0.87, p=0.0000002; NNT 21). Sacubitril/valsartan reduced both primary endpoint components, as well as sudden cardiac death, death due to worsening HF, and death from all causes. Patients on sacubitril/valsartan reported less frequent deterioration of HF and of quality of life, and discontinued study medication less frequently because of an adverse event. PARADIGM-HF demonstrated the superiority of sacubitril/valsartan over enalapril, with a 20% greater impact on cardiovascular mortality compared to ACEIs. Accordingly, in 2016, the European (ESC) and American (ACC/AHA/HFSA) cardiology societies simultaneously issued a class I recommendation for the replacement of ACEIs by sacubitril/valsartan in patients resembling PARADIGM-HF trial participants.info:eu-repo/semantics/publishedVersio

    Candida auris: a quick review on identification, current treatments, and challenges

    Get PDF
    Candida auris is a novel and major fungal pathogen that has triggered several outbreaks in the last decade. The few drugs available to treat fungal diseases, the fact that this yeast has a high rate of multidrug resistance and the occurrence of misleading identifications, and the ability of forming biofilms (naturally more resistant to drugs) has made treatments of C. auris infections highly difficult. This review intends to quickly illustrate the main issues in C. auris identification, available treatments and the associated mechanisms of resistance, and the novel and alternative treatment and drugs (natural and synthetic) that have been recently reported. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.L.C. thanks the Slovak Research and Development Agency under contract No. ˇ APVV-15-0347 and the grant of VEGA 1/0537/19 from the Ministry of Education, Science, Research, and the Sport of the Slovak Republic. C.F.R. would like to acknowledge the UID/EQU/00511/2020 Project—Laboratory of Process Engineering, Environment, Biotechnology and Energy (LEPABE)— financed by national funds through FCT/MCTES (PIDDAC).info:eu-repo/semantics/publishedVersio

    Effectiveness of intensive physiotherapy for gait improvement in stroke: systematic review

    Get PDF
    Introduction: Stroke is one of the leading causes of functional disability worldwide. Approximately 80% of post-stroke subjects have motor changes. Improvement of gait pattern is one of the main objectives of physiotherapists intervention in these cases. The real challenge in the recovery of gait after stroke is to understand how the remaining neural networks can be modified, to be able to provide response strategies that compensate for the function of the affected structures. There is evidence that intensive training, including physiotherapy, positively influences neuroplasticity, improving mobility, pattern and gait velocity in post-stroke recovery. Objectives: Review and analyze in a systematic way the experimental studies (RCT) that evaluate the effects of Intensive Physiotherapy on gait improvement in poststroke subjects. Methodology: Were only included all RCT performed in humans, without any specific age, that had a clinical diagnosis of stroke at any stage of evolution, with sensorimotor deficits and functional gait changes. The databases used were: Pubmed, PEDro (Physiotherapy Evidence Database) and CENTRAL (Cochrane Center Register of Controlled Trials). Results: After the application of the criteria, there were 4 final studies that were included in the systematic review. 3 of the studies obtained a score of 8 on the PEDro scale and 1 obtained a score of 4. The fact that there is clinical and methodological heterogeneity in the studies evaluated, supports the realization of the current systematic narrative review, without meta-analysis. Discussion: Although the results obtained in the 4 studies are promising, it is important to note that the significant improvements that have been found, should be carefully considered since pilot studies with small samples, such as these, are not designed to test differences between groups, in terms of the effectiveness of the intervention applied. Conclusion: Intensive Physiotherapy seems to be safe and applicable in post-stroke subjects and there are indications that it is effective in improving gait, namely speed, travelled distance and spatiotemporal parameters. However, there is a need to develop more RCTs with larger samples and that evaluate the longterm resultsN/

    Redox‐Mediated Amination of Pyrogallol‐Based Polyphenols

    Get PDF
    Flavonoids are known to covalently modify amyloidogenic peptides by amination reactions. The underlying coupling process between polyphenols and N-nucleophiles is assessed by several in vitro and in silico approaches. The coupling reaction involves a sequence of oxidative dearomatization, amination, and reductive amination (ODARA) reaction steps. The C6-regioselectivity of the product is confirmed by crystallographic analysis. Under aqueous conditions, the reaction of baicalein with lysine derivatives yields C−N coupling as well as hydrolysis products of transient imine intermediates. The observed C−N coupling reactions work best for flavonoids combining a pyrogallol substructure with an electron-withdrawing group attached to the C4a-position. Thermodynamic properties such as bond dissociation energies also highlight the key role of pyrogallol units for the antioxidant ability. Combining the computed electronic properties and in vitro antioxidant assays suggests that the studied pyrogallol-containing flavonoids act by various radical-scavenging mechanisms working in synergy. Multivariate analysis indicates that a small number of descriptors for transient intermediates of the ODARA process generates a model with excellent performance (r=0.93) for the prediction of cross-coupling yields. The same model has been employed to predict novel antioxidant flavonoid-based molecules as potential covalent inhibitors, opening a new avenue to the design of therapeutically relevant anti-amyloid compounds

    A dual function of Drosophila capping protein on DE-cadherin maintains epithelial integrity and prevents JNK-mediated apoptosis

    Get PDF
    E-cadherin plays a pivotal role in epithelial cell polarity, cell signalling and tumour suppression. However, how E-cadherin dysfunction promotes tumour progression is poorly understood. Here we show that the actin-capping protein heterodimer, which regulates actin filament polymerization, has a dual function on DE-cadherin in restricted Drosophila epithelia. Knocking down capping protein in the distal wing disc epithelium disrupts DE-cadherin and Armadillo localization at adherens junctions and upregulates DE-cadherin transcription. In turn, DE-cadherin provides an active signal, which prevents Wingless signalling and promotes JNK-mediated apoptosis. However, when cells are kept alive with the Caspase inhibitor P35, the activity of the JNK pathway and of the Yorkie oncogene trigger massive proliferation of cells that fail to stably retain associations with their neighbours. Moreover, loss of capping protein cooperates with the Ras oncogene to induce massive tissue overgrowth. Taken together, our findings argue that in some epithelia, the dual effect of capping protein loss on DE-cadherin triggers the elimination of mutant cells, preventing them from proliferating. However, the appearance of a second mutation that blocks cell death may allow for the development of some epithelial tumour

    Anti-inflammatory and immunoregulatory action of sesquiterpene lactones

    Get PDF
    Sesquiterpene lactones (SL), characterized by their high prevalence in the Asteraceae family, are one of the major groups of secondary metabolites found in plants. Researchers from distinct research fields, including pharmacology, medicine, and agriculture, are interested in their biological potential. With new SL discovered in the last years, new biological activities have been tested, different action mechanisms (synergistic and/or antagonistic effects), as well as molecular structure–activity relationships described. The review identifies the main sesquiterpene lactones with interconnections between immune responses and anti-inflammatory actions, within different cellular models as well in in vivo studies. Bioaccessibility and bioavailability, as well as molecular structure–activity relationships are addressed. Additionally, plant metabolic engineering, and the impact of sesquiterpene lactone extraction methodologies are presented, with the perspective of biological activity enhancement. Sesquiterpene lactones derivatives are also addressed. This review summarizes the current knowledge regarding the therapeutic potential of sesquiterpene lactones within immune and inflammatory activities, highlighting trends and opportunities for their pharmaceutical/clinical use.The authors thank the Regional Development European Foundation and the Alentejo Region Operational Program (ALENTEJO 2020) for their financial support to “MedCynaraBioTec— Selection of Cynara cardunculus genotypes for new Biotechnological applications: the value chain improvement of cardoon, a well-adapted Mediterranean crop” (ALT20-03-0145-FEDER-039495); and “ValBioTecCynara—Economic Valorization of Cardoon (Cynara cardunculus): Study of natural variability and biotechnological applications” project (ALT20-03-0145-FEDER-000038). This work was also funded through FCT under the project UIDB/05183/2020 to the Mediterranean Institute for Agriculture, Environment, and Development (MED)
    corecore