64 research outputs found
Evaluation of MU-MIMO Digital Beamforming Algorithms in B5G/6G LEO Satellite Systems
Satellite Communication (SatCom) systems will be a key component of 5G and 6G networks to achieve the goal of providing unlimited and ubiquitous communications and deploying smart and sustainable networks. To meet the ever-increasing demand for higher throughput in 5G and beyond, aggressive frequency reuse schemes (i.e., full frequency reuse), combined with digital beamforming techniques to cope with the massive co-channel interference, are recognized as a key solution. Aimed at (i) eliminating the joint optimization problem among the beamforming vectors of all users, (ii) splitting it into distinct ones, and (iii) finding a closed-form solution, we propose a beamforming algorithm based on maximizing the users' Signal-to-Leakage-and-Noise Ratio (SLNR) served by a Low Earth Orbit (LEO) satellite. We investigate and assess the performance of several beamforming algorithms, including both those based on Channel State Information (CSI) at the transmitter, i.e., Minimum Mean Square Error (MMSE) and Zero-Forcing (ZF), and those only requiring the users' locations, i.e., Switchable Multi-Beam (MB). Through a detailed numerical analysis, we provide a thorough comparison of the performance in terms of per-user achievable spectral efficiency of the aforementioned beamforming schemes, and we show that the proposed SLNR beamforming technique is able to outperform both MMSE and ZF schemes in the presented SatCom scenario
Evaluation of multi-user multiple-input multiple-output digital beamforming algorithms in B5G/6G low Earth orbit satellite systems
Satellite communication systems will be a key component of 5G and 6G networks to achieve the goal of providing unlimited and ubiquitous communications and deploying smart and sustainable networks. To meet the ever-increasing demand for higher throughput in 5G and beyond, aggressive frequency reuse schemes (i.e., full frequency reuse), combined with digital beamforming techniques to cope with the massive co-channel interference, are recognized as a key solution. Aimed at (i) eliminating the joint optimization problem among the beamforming vectors of all users, (ii) splitting it into distinct ones, and (iii) finding a closed-form solution, we propose a beamforming algorithm based on maximizing the users' signal-to-leakage-and-noise ratio served by a low Earth orbit satellite. We investigate and assess the performance of several beamforming algorithms, including both those based on channel state information at the transmitter, that is, minimum mean square error and zero forcing, and those only requiring the users' locations, that is, switchable multi-beam. Through a detailed numerical analysis, we provide a thorough comparison of the performance in terms of per-user achievable spectral efficiency of the aforementioned beamforming schemes, and we show that the proposed signal to-leakage-plus-noise ratio beamforming technique is able to outperform both minimum mean square error and multi-beam schemes in the presented satellite communication scenario
A pathogenic tau fragment compromises microtubules, disrupts insulin signaling and induces the unfolded protein response
Human tauopathies including Alzheimer’s disease, progressive supranuclear palsy and related disorders, are
characterized by deposition of pathological forms of tau, synaptic dysfunction and neuronal loss. We have previously
identified a pathogenic C-terminal tau fragment (Tau35) that is associated with human tauopathy. However, it is not
known how tau fragmentation affects critical molecular processes in cells and contributes to impaired physiological
function. Chinese hamster ovary (CHO) cells and new CHO cell lines stably expressing Tau35 or full-length human tau
were used to compare the effects of disease-associated tau cleavage on tau function and signaling pathways. Western
blots, microtubule-binding assays and immunofluorescence labeling were used to examine the effects of Tau35 on tau
function and on signaling pathways in CHO cells. We show that Tau35 undergoes aberrant phosphorylation when
expressed in cells. Although Tau35 contain the entire microtubule-binding region, the lack of the amino terminal half
of tau results in a marked reduction in microtubule binding and defective microtubule organization in cells. Notably,
Tau35 attenuates insulin-mediated activation of Akt and a selective inhibitory phosphorylation of glycogen synthase
kinase-3. Moreover, Tau35 activates ribosomal protein S6 kinase beta-1 signaling and the unfolded protein response,
leading to insulin resistance in cells. Tau35 has deleterious effects on signaling pathways that mediate pathological
changes and insulin resistance, suggesting a mechanism through which N-terminal cleavage of tau leads to the
development and progression of tau pathology in human tauopathy. Our findings highlight the importance of the Nterminal region of tau for its normal physiological function. Furthermore, we show that pathogenic tau cleavage
induces tau phosphorylation, resulting in impaired microtubule binding, disruption of insulin signaling and activation
of the unfolded protein response. Since insulin resistance is a feature of several tauopathies, this work suggests new
potential targets for therapeutic intervention
Reliability of Magnetic Resonance Imaging (MRI) scoring of the metatarsophalangeal joints of the foot according to the Rheumatoid Arthritis MRI Score
Objective. The Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) is validated for hand MRI. Its reliability applied to metatarsophalangeal (MTP 1-5) joints is unknown and was studied in early arthritis and clinically suspect arthralgia.Methods. Patients underwent 1.5 Tesla MRI of MTP, metacarpophalangeal (MCP 2-5), and wrist joints. Two paired readers scored bone marrow edema (BME), synovitis, tenosynovitis, and erosions. Interreader reliability was assessed of 441 consecutive early arthritis patients at baseline, 215 by 2 readers, and the remaining 226 by 2 different readers. Two readers scored baseline MRI of 82 consecutive patients with clinically suspect arthralgia, and 40 randomly selected patients by 9 readers. Intrareader reliability was determined on a random set of 15 early arthritis patients, scored twice by 2 readers. For change scores, 30 early arthritis patients with baseline and 1-year followup MRI were scored by 2 readers. Intraclass correlation coefficients (ICC), Bland-Altman (BA) plots, and smallest detectable change (SDC) were determined. MRI data of MTP joints were compared to wrist and MCP joints.Results. Interreader ICC and mean scores in early arthritis were BME ICC 0.91-0.92 (mean 1.5 +/- SD 2.6), synovitis 0.90-0.92 (1.3 +/- 1.7), tenosynovitis 0.80-0.85 (1.1 +/- 1.8), and erosions 0.88-0.89 (0.7 +/- 1.0). In patients with clinically suspect arthralgia, ICC were comparable. Intrareader ICC for inflammatory MRI features were 0.84-0.98, for erosions 0.71 (reader 1), and 0.92 (reader 2). Change score ICC were = 0.90, except erosions (0.77). SDC were = 1.0. BA plots showed no systematic bias. Reliability scores of MTP joints were similar to MCP and wrist joints.Conclusion. Status and change MRI scores of BME, synovitis, tenosynovitis, and erosions of MTP joints can be assessed reliably by RAMRIS.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas
Truncated tau interferes with the autophagy and endolysosomal pathway and results in lipid accumulation
This is the final version. Available from Springer via the DOI in this record. Availability of data and material.
The data that support the findings of this study are available from the corresponding author upon reasonable request.The autophagy-lysosomal pathway plays a critical role in the clearance of tau protein aggregates that deposit in the brain in tauopathies, and defects in this system are associated with disease pathogenesis. Here, we report that expression of Tau35, a tauopathy-associated carboxy-terminal fragment of tau, leads to lipid accumulation in cell lines and primary cortical neurons. Our findings suggest that this is likely due to a deleterious block of autophagic clearance and lysosomal degradative capacity by Tau35. Notably, upon induction of autophagy by Torin 1, Tau35 inhibited nuclear translocation of transcription factor EB (TFEB), a key regulator of lysosomal biogenesis. Both cell lines and primary cortical neurons expressing Tau35 also exhibited changes in endosomal protein expression. These findings implicate autophagic and endolysosomal dysfunction as key pathological mechanisms through which disease-associated tau fragments could lead to the development and progression of tauopathy
Safeguarding people living in vulnerable conditions in the COVID-19 era through universal health coverage and social protection
The COVID-19 pandemic is unprecedented. The pandemic not only induced a public health crisis, but has led to severe economic, social, and educational crises. Across economies and societies, the distributional consequences of the pandemic have been uneven. Among groups living in vulnerable conditions, the pandemic substantially magnified the inequality gaps, with possible negative implications for these individuals' long-term physical, socioeconomic, and mental wellbeing. This Viewpoint proposes priority, programmatic, and policy recommendations that governments, resource partners, and relevant stakeholders should consider in formulating medium-term to long-term strategies for preventing the spread of COVID-19, addressing the virus's impacts, and decreasing health inequalities. The world is at a never more crucial moment, requiring collaboration and cooperation from all sectors to mitigate the inequality gaps and improve people's health and wellbeing with universal health coverage and social protection, in addition to implementation of the health in all policies approach
The choice between a ritonavir-boosted protease inhibitor- and a non-nucleoside reverse transcriptase inhibitor-based regimen for initiation of antiretroviral treatment – results from an observational study in Germany
Detection of Echinococcus multilocularis in Carnivores in Razavi Khorasan Province, Iran Using Mitochondrial DNA
Echinococcus multilocularis causes alveolar echinococcosis, a serious zoonotic disease present in many areas of the world. The parasite is maintained in nature through a life cycle in which adult worms in the intestine of carnivores transmit infection to small mammals, predominantly rodents, via eggs in the feces. Humans may accidentally ingest eggs of E. multilocularis through contact with the definitive host or by direct ingestion of contaminated water or foods, causing development of a multivesicular cyst in the viscera, especially liver and lung. We found adult E. multilocularis in the intestine and/or eggs in feces of all wild carnivores examined and in some stray and domestic dogs in villages of Chenaran region, northeastern Iran. The life cycle of E. multilocularis is being maintained in this area by wild carnivores, and the local population and visitors are at risk of infection with alveolar echinococcosis. Intensive health initiatives for control of the parasite and diagnosis of this potentially fatal disease in humans, in this area of Iran, are needed
Knowledge, attitudes and practices with regard to the presence, transmission, impact, and control of cystic echinococcosis in Sidi Kacem Province, Morocco
BACKGROUND: This study is a component of a large research project on five major neglected zoonotic diseases (NZDs) including cystic echinococcosis and was undertaken in the Province of Sidi Kacem over a period of four years (April 2009-March 2013). METHODS: Questionnaires were administered at community level in a total of 27 communes and visits were made to all of the 10 abattoirs situated in the Province, to collect qualitative data on determinants of transmission for disease in humans and animals. More specifically, community knowledge, attitudes and practices related to cystic echinococcosis were assessed, as well as the extent to which local customs and behaviours may promote transmission. Abattoir infrastructure and practices, and their role in perpetuating disease transmission were also critically evaluated. RESULTS: The results show that only 50 % of people have heard of the disease, and of those, only 21 % are aware of the dog’s role in disease transmission. Sixty-seven per cent of respondents stated that dogs are fed ruminant organs deemed unfit for human consumption. Owned dogs have access to the family home, including the kitchen, in 39 % of households. The extent of this close proximity between humans and animals is even more pertinent when one considers that dogs are omnipresent in the community, with an average of 1.8 dogs owned per household. The unrestricted access of dogs to abattoirs is a huge issue, which further promotes disease transmission. CONCLUSION: This study would suggest that the high prevalence of cystic echinococcosis in humans and animals in Morocco is largely due to three factors: 1) abundance of dogs 2) engagement in risky behaviour of the local population and 3) poor abattoir infrastructure and practices. This has serious implications in terms of the socio-economic impact of the disease, especially for rural poor communities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-015-0082-9) contains supplementary material, which is available to authorized users
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