478 research outputs found

    Dispersion relation for electron waves propagating in an isotropic plasma containing Maxwellian and suprathermal electrons

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    The paper discusses the dispersion relation for longitudinal electron waves propagating in a collisionless, homogeneous isotropic plasma, which contains both Maxwellian and suprathermal electrons. I t is found that the dispersion curve, known to have two separate branches for zero suprathermal energy spread,depends sensitively on this quantity. As the energy half-width of the suprathermal population increases, the branches approach each other until they touch at a connexion point, for a small critical value of that half-width. The topology of the dispersion curves is different for half-widths above and below critical; and this can affect the use of wave-propagation measurements as a diagnostic technique for the determination of the electron distribution function. Both the distance between the branches and spatial damping near the connexion frequency depend on the half-width, if below critical, and can be used to determine it. The theory is applied to experimental data

    The ferroelectric Mott-Hubbard phase of organic (TMTTF)2X conductors

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    We present experimental evidences for a ferro-electric transition in the family of quasi one- dimensional conductors (TMTTF)2X. We interpret this new transition in the frame of the combined Mott-Hubbard state taking into account the double action of the spontaneous charge disproportionation on the TMTTF molecular stacks and of the X anionic potentials

    The Propulsive Small Expendable Deployer System Experiment

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    Relatively short electrodynamic tethers can extract orbital energy to 'push' against a planetary magnetic field to achieve propulsion without the expenditure of propellant. The Propulsive Small Expendable Deployer System experiment will use the flight-proven Small Expendable Deployer System (SEDS) to deploy a 5 km bare copper tether from a Delta II upper stage to achieve approximately 0.4 N drag thrust, thus lowering the altitude of the stage. The experiment will use a predominantly 'bare' tether for current collection in lieu of the endmass collector and insulated tether approach used on previous missions. The flight experiment is a precursor to a more ambitious electrodynamic tether upper stage demonstration mission which will be capable of orbit raising, lowering and inclination changes - all using electrodynamic thrust. The expected performance of the tether propulsion system during the experiment is described

    Oxygen-Driven Tumour Growth Model : A Pathology-Relevant Mathematical Approach

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    We acknowledge Lucas Dias Fernandes and Dr Nicolas Rubido from the University of Aberdeen and Dr Neil Evans from the University of Warwick for the broad discussions on the mathematics.Peer reviewedPublisher PD

    Novel methylselenoesters induce programed cell death via entosis in pancreatic cancer cells

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    Redox active selenium (Se) compounds have gained substantial attention in the last decade as potential cancer therapeutic agents. Several Se compounds have shown high selectivity and sensitivity against malignant cells. The cytotoxic effects are exerted by their biologically active metabolites, with methylselenol (CH3SeH) being one of the key executors. In search of novel CH3SeH precursors, we previously synthesized a series of methylselenoesters that were active (GI50 < 10 µM at 72 h) against a panel of cancer cell lines. Herein, we refined the mechanism of action of the two lead compounds with the additional synthesis of new analogs (ethyl, pentyl, and benzyl derivatives). A novel mechanism for the programmed cell death mechanism for Se-compounds was identified. Both methylseleninic acid and the novel CH3SeH precursors induced entosis by cell detachment through downregulation of cell division control protein 42 homolog (CDC42) and its downstream effector β1-integrin (CD29). To our knowledge, this is the first time that Se compounds have been reported to induce this type of cell death and is of importance in the characterization of the anticancerogenic properties of these compounds

    A diphenyldiselenide derivative induces autophagy via JNK in HTB-54 lung cancer cells

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    Symmetric aromatic diselenides are potential anticancer agents with strong cytotoxic activity. In this study, the in vitro anticancer activities of a novel series of diarylseleno derivatives from the diphenyldiselenide (DPDS) scaffold were evaluated. Most of the compounds exhibited high efficacy for inducing cytotoxicity against different human cancer cell lines. DPDS 2, the compound with the lowest mean GI50 value, induced both caspase-dependent apoptosis and arrest at the G0/G1 phase in acute lymphoblastic leucemia CCRF-CEM cells. Consistent with this, PARP cleavage; enhanced caspase-2, -3, -8 and -9 activity; reduced CDK4 expression and increased levels of p53 were detected in these cells upon DPDS 2 treatment. Mutated p53 expressed in CCRF-CEM cells retains its transactivating activity. Therefore, increased levels of p21CIP1 and BAX proteins were also detected. On the other hand, DPDS 6, the compound with the highest selectivity index for cancer cells, resulted in G2/M cell cycle arrest and caspase-independent cell death in p53 deficient HTB-54 lung cancer cells. Autophagy inhibitors 3-methyladenine, wortmannin and chloroquine inhibited DPDS 6-induced cell death. Consistent with autophagy, increased LC3-II and decreased SQSTM1/p62 levels were detected in HTB-54 cells in response to DPDS 6. Induction of JNK phosphorylation and a reduction in phospho-p38 MAPK were also detected. Moreover, the JNK inhibitor SP600125-protected HTB-54 cells from DPDS 6-induced cell death indicating that JNK activation is involved in DPDS 6-induced autophagy. These results highlight the anticancer effects of these derivatives and warrant future studies examining their clinical potential

    Use of Biomarkers to Improve 28-Day Mortality Stratification in Patients with Sepsis and SOFA ≤ 6

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    Molecular diagnosis; Mortality; Sepsis biomarkersDiagnóstico molecular; Mortalidad; Biomarcadores de sepsisDiagnòstic molecular; Mortalitat; Biomarcadors de sèpsiaEarly diagnosis and appropriate treatments are crucial to reducing mortality risk in septic patients. Low SOFA scores and current biomarkers may not adequately discern patients that could develop severe organ dysfunction or have an elevated mortality risk. The aim of this prospective observational study was to evaluate the predictive value of the biomarkers mid-regional pro-adrenomedullin (MR-proADM), procalcitonin (PCT), C-reactive protein (CRP), and lactate for 28-day mortality in patients with sepsis, and patients with a SOFA score ≤6. 284 were included, with a 28-day all-cause mortality of 8.45% (n = 24). Non-survivors were older (p = 0.003), required mechanical ventilation (p = 0.04), were ventilated for longer (p = 0.02), and had higher APACHE II (p = 0.015) and SOFA (p = 0.027) scores. Lactate showed the highest predictive ability for all-cause 28-day mortality, with an area under the receiver-operating characteristic curve (AUROC) of 0.67 (0.55–0.79). The AUROC for all-cause 28-day mortality in patients with community-acquired infection was 0.69 (0.57–0.84) for SOFA and 0.70 (0.58–0.82) for MR-proADM. A 2.1 nmol/L cut-off point for this biomarker in this subgroup of patients discerned, with 100% sensibility, survivors from non-survivors at 28 days. In patients with community-acquired sepsis and initial SOFA score ≤ 6, MR-proADM could help identify patients at risk of 28-day mortality.This research was funded by a restricted grant from Thermo Fisher (Hennigsdorf, Germany), consisting of free-of-charge kits. However, the funding organization had no role in the collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication

    Precision medicine in sepsis and septic shock: From omics to clinical tools

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    Endotype; Organ dysfunction; SepsisEndotipo; Disfunción de órganos; SepsisEndotip; Disfunció d'òrgans; SèpsiaSepsis is a heterogeneous disease with variable clinical course and several clinical phenotypes. As it is associated with an increased risk of death, patients with this condition are candidates for receipt of a very well-structured and protocolized treatment. All patients should receive the fundamental pillars of sepsis management, which are infection control, initial resuscitation, and multiorgan support. However, specific subgroups of patients may benefit from a personalized approach with interventions targeted towards specific pathophysiological mechanisms. Herein, we will review the framework for identifying subpopulations of patients with sepsis, septic shock, and multiorgan dysfunction who may benefit from specific therapies. Some of these approaches are still in the early stages of research, while others are already in routine use in clinical practice, but together will help in the effective generation and safe implementation of precision medicine in sepsis

    Label-Free Plasmonic Biosensor for Rapid, Quantitative, and Highly Sensitive COVID-19 Serology: Implementation and Clinical Validation

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    COVID-19; Biosensor plasmónico; SerologíaCOVID-19; Biosensor plasmònic; SerologiaCOVID-19; Plasmonic biosensor; SerologySerological tests are essential for the control and management of COVID-19 pandemic (diagnostics and surveillance, and epidemiological and immunity studies). We introduce a direct serological biosensor assay employing proprietary technology based on plasmonics, which offers rapid (<15 min) identification and quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in clinical samples, without signal amplification. The portable plasmonic device employs a custom-designed multiantigen (RBD peptide and N protein) sensor biochip and reaches detection limits in the low ng mL–1 range employing polyclonal antibodies. It has also been implemented employing the WHO-approved anti-SARS-CoV-2 immunoglobulin standard. A clinical validation with COVID-19 positive and negative samples (n = 120) demonstrates its excellent diagnostic sensitivity (99%) and specificity (100%). This positions our biosensor as an accurate and easy-to-use diagnostics tool for rapid and reliable COVID-19 serology to be employed both at laboratory and decentralized settings for the disease management and for the evaluation of immunological status during vaccination or treatment.ICN2 and UVE acknowledge financial support from H2020 Research and Innovation Programme of the European Commission (H202-SC1-PHE-Coronavirus-2020, CONVAT Project, No. 101003544). The ICN2 is funded by the CERCA program/Generalitat de Catalunya and supported by the Severo Ochoa Centres of Excellence program funded by the Spanish Research Agency (AEI, grant no. SEV-2017-0706). ICN2 group is very grateful to EPI Industries (Barcelona, Spain) for its kind donation supporting our research in COVID-19. O.C.-L. acknowledges the economic support from the Spanish Ministry of Science and Innovation and the Spanish Research Agency and the European Social Fund (ESF) (ref. BES-2017-080527) linked to the TEC 2016-78515-R project Predict. A part of the work was supported by the European Virus Archive GLOBAL (EVA-GLOBAL) project that has received funding from the EU Horizon 2020 (grant agreement No. 871029). A.T. and L.F.-B. acknowledge financial support from GENCAT-DGRIS COVID. We are indebted to all the patients who accepted to participate contributing to science advancement. We are indebted to the HCB-IDIBAPS Biobank for the human samples and data procurement and to the Fundació Glòria Soler for its support to the COVIDBANK collection. We thank the IDIBAPS Biobank for its valuable contribution to sample processing and storage. The authors acknowledge the EU Horizon 2020 Program under grant agreement no. 644956 (RAIS project) for funding the Hospital Vall d’Hebron Biobank. The VHIR-HUVH is supported by Plan Nacional de I + D + i 2013-2016 and ISCIII-Ministerio de Ciencia e Innovación, and Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003)─cofinanced by European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 2014. Part of the samples and data from patients included in this study were provided by the Vall d’Hebron University Hospital Biobank (PT17/0015/0047), integrated in the Spanish National Biobanks Network, and they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. The authors kindly appreciate the generous donation of samples and clinical data of the donors of the Sepsis Bank of HUVH Biobank and COVID-19 patients attended at HUVH
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