528 research outputs found
Non-topological solitons in field theories with kinetic self-coupling
We investigate some fundamental features of a class of non-linear
relativistic lagrangian field theories with kinetic self-coupling. We focus our
attention upon theories admitting static, spherically symmetric solutions in
three space dimensions which are finite-energy and stable. We determine general
conditions for the existence and stability of these non-topological soliton
solutions. In particular, we perform a linear stability analysis that goes
beyond the usual Derrick-like criteria. On the basis of these considerations we
obtain a complete characterization of the soliton-supporting members of the
aforementioned class of non-linear field theories. We then classify the family
of soliton-supporting theories according to the central and asymptotic
behaviors of the soliton field, and provide illustrative explicit examples of
models belonging to each of the corresponding sub-families. In the present work
we restrict most of our considerations to one and many-components scalar
models. We show that in these cases the finite-energy static spherically
symmetric solutions are stable against charge-preserving perturbations,
provided that the vacuum energy of the model vanishes and the energy density is
positive definite. We also discuss briefly the extension of the present
approach to models involving other types of fields, but a detailed study of
this more general scenario will be addressed in a separate publication.Comment: 5 pages, 1 figure, revtex4, minor corrections adde
Soliton solutions in relativistic field theories and gravitation
We report on some recent results on a class of relativistic lagrangian field
theories supporting non-topological soliton solutions and their applications in
the contexts of Gravitation and Cosmology. We analyze one and many-components
scalar fields and gauge fields.Comment: Latex, 4 pages, 1 figure. Talk given at 30th Spanish Relativity
Meeting (ERE 2007): Relativistic Astrophysics and Cosmology, Puerto de la
Cruz, Tenerife, Spain, 10-14 Sep 200
Screening effects in Relativistic Models of Dense Matter at Finite Temperature
We investigate screening effects of the medium on the potential interaction
between two static 'charges' for different models of dense plasmas in the
one-boson exchange approximation. The potential can exhibit an oscillatory
behavior, which is related to the analytic structure of the corresponding boson
propagators in the complex -plane. We have first revisited the one-pion
exchange in a nuclear medium. In addition to Friedel oscillations, which are
associated to branch cuts in the -plane, there appears another oscillatory
component, which arises from a pole on the pion propagator. This pole is
located appart from the axes, giving rise to an oscillating Yukawa-like
potential. Therefore, we call this phenomenon 'Yukawa oscillations'. This
phenomenon does not appear in the Debye component of the QED screened
potential, even if the coupling constant is artificially increased. We have
also studied a model of QCD quark-gluon plasma. In this case, the one-gluon
propagator also shows this kind of poles. At high densities and/or
temperatures, where one expects perturbative QCD to be valid, the pole shifts
towards large momenta.Comment: Revtex. 9 pages, 9 figure
Generalized gauge field theories with non-topological soliton solutions
We perform a systematic analysis of the conditions under which
\textit{generalized} gauge field theories of compact semisimple Lie groups
exhibit electrostatic spherically symmetric non-topological soliton solutions
in three space dimensions. By the term \textit{generalized}, we mean that the
dynamics of the concerned fields is governed by lagrangian densities which are
general functions of the quadratic field invariants, leading to physically
consistent models. The analysis defines exhaustively the class of this kind of
lagrangian models supporting those soliton solutions and leads to methods for
their explicit determination. The necessary and sufficient conditions for the
linear stability of the finite-energy solutions against charge-preserving
perturbations are established, going beyond the usual Derrick-like criteria,
which only provides necessary conditions.Comment: 6 pages, revtex
Friedel Oscillations in Relativistic Nuclear Matter
We calculate the low-momentum N-N effective potential obtained in the OBE
approximation, inside a nuclear plasma at finite temperature, as described by
the relativistic - model. We analyze the screening effects
on the attractive part of the potential in the intermediate range as density or
temperature increase. In the long range the potential shows Friedel-like
oscillations instead of the usual exponential damping. These oscillations arise
from the sharp edge of the Fermi surface and should be encountered in any
realistic model of nuclear matter.Comment: 11 pages in preprint format, typeset using REVTEX, 3 included figures
in tar, compressed, uuencoded forma
1118-78 Primary angioplasty versus facilitated intervention (tenecteplase plus stenting) in patients with ST elevated acute myocardial infarction: Final results of the GRACIA-2 trial
Selectively Targeting Breast Cancer Stem Cells by 8-Quinolinol and Niclosamide
Cancer stem cells; Combination therapy; NiclosamideCélulas madre cancerosas; Terapia combinada; NiclosamidaCèl·lules mare cancerígenes; Teràpia combinada; NiclosamidaCancer maintenance, metastatic dissemination and drug resistance are sustained by cancer stem cells (CSCs). Triple negative breast cancer (TNBC) is the breast cancer subtype with the highest number of CSCs and the poorest prognosis. Here, we aimed to identify potential drugs targeting CSCs to be further employed in combination with standard chemotherapy in TNBC treatment. The anti-CSC efficacy of up to 17 small drugs was tested in TNBC cell lines using cell viability assays on differentiated cancer cells and CSCs. Then, the effect of 2 selected drugs (8-quinolinol -8Q- and niclosamide -NCS-) in the cancer stemness features were evaluated using mammosphere growth, cell invasion, migration and anchorage-independent growth assays. Changes in the expression of stemness genes after 8Q or NCS treatment were also evaluated. Moreover, the potential synergism of 8Q and NCS with PTX on CSC proliferation and stemness-related signaling pathways was evaluated using TNBC cell lines, CSC-reporter sublines, and CSC-enriched mammospheres. Finally, the efficacy of NCS in combination with PTX was analyzed in vivo using an orthotopic mouse model of MDA-MB-231 cells. Among all tested drug candidates, 8Q and NCS showed remarkable specific anti-CSC activity in terms of CSC viability, migration, invasion and anchorage independent growth reduction in vitro. Moreover, specific 8Q/PTX and NCS/PTX ratios at which both drugs displayed a synergistic effect in different TNBC cell lines were identified. The sole use of PTX increased the relative presence of CSCs in TNBC cells, whereas the combination of 8Q and NCS counteracted this pro-CSC activity of PTX while significantly reducing cell viability. In vivo, the combination of NCS with PTX reduced tumor growth and limited the dissemination of the disease by reducing circulating tumor cells and the incidence of lung metastasis. The combination of 8Q and NCS with PTX at established ratios inhibits both the proliferation of differentiated cancer cells and the viability of CSCs, paving the way for more efficacious TNBC treatments.This work was supported by the Instituto de Salud Carlos III (ISCiii), through Networking Research Center on Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), an initiative that also counts with the assistance from the European Regional Development Fund (ERDF), specifically in the PENTRI-2 Project and by the “Fundació Marató TV3” (337/C/2013) to I.A., M.R. and E.V. Our laboratories were also supported by the Fondo de Investigaciones Sanitarias (FIS, grants PI20/1474 to S.S.J. and PI18/00871 and PI21/00936), co-financed by the ERDF and the 2017-SGR-638 of the Catalan Government to S.S.J. and EvoNano Project (GA800983), funded by European Union’s Horizon 2020 FET Open Programme. N.G.-A. was supported by grants from Pla Estratègic de Recerca i Innovació en Salut (PERIS) of Catalonia (SLT006/17/00270 270)
Endoglin and MMP14 contribute to Ewing sarcoma spreading by modulation of cell-matrix interactions
Endoglin (ENG) is a mesenchymal stem cell (MSC) marker typically expressed by active endothelium. This transmembrane glycoprotein is shed by matrix metalloproteinase 14 (MMP14). Our previous work demonstrated potent preclinical activity of first-in-class anti-ENG antibody-drug conjugates as a nascent strategy to eradicate Ewing sarcoma (ES), a devastating rare bone/soft tissue cancer with a putative MSC origin. We also defined a correlation between ENG and MMP14 expression in ES. Herein, we show that ENG expression is significantly associated with a dismal prognosis in a large cohort of ES patients. Moreover, both ENG/MMP14 are frequently expressed in primary ES tumors and metastasis. To deepen in their functional relevance in ES, we conducted transcriptomic and proteomic profiling of in vitro ES models that unveiled a key role of ENG and MMP14 in cell mechano-transduction. Migration and adhesion assays confirmed that loss of ENG disrupts actin filament assembly and filopodia formation, with a concomitant effect on cell spreading. Furthermore, we observed that ENG regulates cell-matrix interaction through activation of focal adhesion signaling and protein kinase C expression. In turn, loss of MMP14 contributed to a more adhesive phenotype of ES cells by modulating the transcriptional extracellular matrix dynamics. Overall, these results suggest that ENG and MMP14 exert a significant role in mediating correct spreading machinery of ES cells, impacting the aggressiveness of the disease.E.A.’s laboratory is supported by ISCIII-FEDER (PI20/00003), CIBERONC (CB16/12/00361), PAIDI-Junta de Andalucía (P18-RT-735), Fundación CRIS Contra el Cáncer, Asociación Candela Riera and Asociación Pablo Ugarte. A.T.A. is supported by Juan de la Cierva Incorporación fellowship (IJC-2018-036767-I); P.P.-C. is sponsored by the Fundación María García Estrada. J.O.-P is supported by Ph.D. Grant Plan Propio from the University of Seville. J.D.-M is supported by CIBERONC (CB16/12/00361). C.S.-A. is supported by the European Social Fund and the Junta de Andalucía (Talento Doctores 2020, DOC_01473). This work was supported by grants from the Consejería de Salud (Junta de Andalucía, grants No PI-0036-2017, PI-0040-2017, and PI-0061-2020) awarded to J.D.-M, A.T.A. and C. S.-A., respectively. This work was also supported by the GEIS-Fundación Mari Paz Jiménez Casado (IV beca trienal) granted to J.D.-M, the 13ª GEIS-Beca Buesa granted to A.T.A. and CRIS (Cancer Research Innovation Spain) granted to J.D.-M and E.A. The laboratory of T.G.P.G. is supported by the Barbara and Wilfried Mohr Foundation. The lab of J.A. is supported by the Instituto de Salud Carlos III (ISCIII), grant number PI20CIII/00020; Asociación Pablo Ugarte, grant numbers TRPV205/18, TPI-M 1149/13; Asociación Candela Riera; Asociación Todos Somos Iván & Fundación Sonrisa de Alex, grant reference: TVP333-19.S
Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)
Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters.
Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs).
Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001).
Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio
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