93 research outputs found
On the traces of the solutions of the anisotropic hyperbolic heat equation with irregular heat sources
No full textWe present some results about the traces of solutions of the anisotropic hyperbolic heat equation over the boundary of cylindrical open sets of types Ω x ]0, T [ and Ωx ]0, ∞[, when the heat sources are irregular distributions.Partially supported by the PAID-06-11 UPV grant, Ref. 1988.
The research for the first named author was partially supported by Generalitat Valenciana, Conselleria d'Educació, Cultura i Esport, Spain, Grant PROMETEO/2013/058.López Molina, JA.; Trujillo Guillen, M. (2013). On the traces of the solutions of the anisotropic hyperbolic heat equation with irregular heat sources. Far East Journal of Applied mathematics. 81(1-2):65-87. https://riunet.upv.es/handle/10251/58974S6587811-
Regularity of solutions of the anisotropic hyperbolic heat equation with non regular heat sources and homogeneous boundary conditions
No full text[EN] We study regularity properties for the solution of homogeneous boundary value problems for the anisotropic
hyperbolic heat equation in the case of in nitely differentiable coefficients but irregular distributions as internal heat
sources.The research of this author was partially supported by Generalitat Valenciana, Conselleria d'Educacio, Cultura i Esport, Spain, Grant PROMETEO/2013/058.López Molina, JA.; Trujillo Guillen, M. (2017). Regularity of solutions of the anisotropic hyperbolic heat equation with non regular heat
sources and homogeneous boundary conditions. Turkish Journal of Mathematics. 41(3):461-482. https://doi.org/10.3906/mat-1502-9S46148241
Hydro-meteorological trigger conditions of debris flows in Austria
No full textDifferent factors influence the disposition of a watershed for initiation of debris flows, including meteorological trigger conditions as well as the hydrologic and geomorphic disposition. The latter includes slowly changing factors like relief energy or sediment availability, whereas the hydrologic state of a watershed may vary over short time scales. This contribution summarizes the outcomes of a long term project to quantify meteorological and hydrological trigger conditions leading to debris flows at different temporal and spatial scales in the Austrian Alps. The analysis employs a database of more than 4,500 debris flows over the last 100+ years, which is the period for which systematic rainfall data is available. A Bayesian analysis was carried out for determining occurrence probabilities for all Austria. For selected regions, hydrological trigger conditions were assessed using a semi-distributed, conceptual rainfall-runoff model, which was calibrated to measured runoff data. As expected we find increasing trigger probabilities with increasing rainfall amounts and intensities. However, the additional information of regional hydrological parameters as well as their temporal evolution over days prior to a debris-flow event, enables to capture different trigger conditions, including short duration rainstorms, long lasting rainfall events, and snow melt. We also find that a trigger-type resolved prediction of debris-flow susceptibility based on the hydro-meteorological catchment information is superior to simple rainfall-only approaches. The results of this analysis shall improve our understanding of long-term trigger conditions and trends of extreme mass wasting processes in the Alps and aim to become a valuable tool in engineering hazard assessment.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Water Resource
Characterization of novel small molecule inhibitors of FOXM1 as potential therapeutic agents for breast cancer
No full textBreast cancer is the most common cancer in women in the United States and the second leading cause of cancer death among women. Despite significant advances in the treatment of breast cancer, few solutions exist addressing the challenges of hormone resistance, recurrence, and metastasis, highlighting the urgent need for new molecular targets and therapies. Forkhead box M1 (FOXM1) is a cell cycle associated transcription factor that is remarkably overexpressed in breast cancers and has a biological role in all hallmarks of cancer development, from oncogenic transformation to treatment resistance and metastasis. Inhibition of FOXM1 through small interfering RNA (siRNA) depletion and other modes abrogates its cancer promoting effects, bringing FOXM1 forth as a promising target in the treatment of breast and other cancers. Despite this compelling evidence, no inhibitors of FOXM1 that have therapeutic potential have emerged due to lack of specificity and potency, and importantly, poor pharmacokinetic profiles in animals. To this end, we have identified and characterized novel inhibitors of FOXM1 that effectively suppress breast cancer cell growth and survival in vitro and in vivo. Our potential FOXM1 inhibitors displayed significantly improved potency compared to other inhibitors, as well as strong pharmacokinetic profiles with both oral and subcutaneous activity. In breast cancer xenograft models, our FOXM1 inhibitors suppressed tumor growth at both high and low dose regimens with concurrent downregulation of FOXM1 target genes.
We showed that our inhibitors bind the FOXM1 protein directly and decrease its stability, resulting in the downregulation of FOXM1 protein level. Genome-wide RNA-Seq studies revealed that these inhibitors modulate expression of FOXM1-regulated transcription networks in breast cancer cells. In addition, gene networks related to the known role of FOXM1 as a master regulator of the cell cycle, including G1/S and G2/M transition, execution of S-phase and mitotic processes, DNA damage repair, and apoptosis were impacted. Consistent with this, treatment of breast cancer cells with our inhibitors results in G2/M cell cycle arrest and apoptosis via caspase 3/7 activation. Breast cancer cells selected for resistance to our lead compound NB-73 displayed a remarkable reversal of the inhibition of FOXM1-regulated gene expression and cell cycle-related pathways seen in wild type cells after treatment, reflecting the importance of these pathways to the molecular mechanism of the compound.
Chemotherapy is still the only treatment available for triple negative breast cancers lacking druggable targets. Triple negative breast cancers overexpress FOXM1 compared to other breast cancer subtypes, making targeting FOXM1 particularly important in this context. Since combination therapy is the standard of care in cancer treatment, we assessed the potential of combining our novel FOXM1 inhibitors with drugs currently used to treat cancer or in clinical development to inhibit triple negative breast cancers. Our FOXM1 inhibitors synergistically suppressed triple negative breast cancer cells in combination with drugs from several classes, including cyclin-dependent kinase inhibitors, proteasome inhibitors, and others. The combination of FOXM1 inhibitors with Bortezomib, a proteasome inhibitor, displayed particularly strong inhibition of MDA-MB-231 cells through induction of G2/M arrest and apoptosis. In Rb-expressing cells MDA-MB-231 cells, the CDK4/6 inhibitor Abemaciclib synergized with our FOXM1 inhibitors to potently suppress cell proliferation. Thus, in this work we present compounds that display strong translational potential through their FOXM1-specific activity, pharmacokinetic and antitumor activity, and synergistic interaction with targeted therapies.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2022-12-01The student, Valeria Sanabria Guillen, accepted the attached license on 2020-11-24 at 11:08.The student, Valeria Sanabria Guillen, submitted this Dissertation for approval on 2020-11-24 at 11:18.This Dissertation was approved for publication on 2020-11-25 at 14:40.DSpace SAF Submission Ingestion Package generated from Vireo submission #15950 on 2021-03-04 at 16:32:22Made available in DSpace on 2021-03-05T21:45:36Z (GMT). No. of bitstreams: 2
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The relativistic theory of gravitation beyond general relativity
No full textIt presents the basics of the “Relativistic theory of gravitation”, with the inclusion of original texts, from various papers, published between 1987 and 2009, by theirs authors: S. S Gershtein, A. A. Logunov, Yu. M. Loskutov and M. A. Mestvirishvili, additionally, together with the introductions, summaries and conclusions of the author of this paper.
The “Relativistic theory of gravitation” is a gauge theory, compatible with the theories of quantum physics of the electromagnetic, weak and strong forces, which defines gravity as the fourth force existing in nature, as a static field equipped with the transmitter particles of the virtual gravitons of spins 2 and 0, within the spirit of Galilei's principle of relativity, in his generalization of Poincaré's Special Relativity that allowed the authors to universalize that the physical laws of nature are complied with regardless of the frames of reference where they apply, integrated into the Grossmann-Einstein Entwurf theory, in its further development, by those authors, therefore, this theory preserves the conservation laws of energy-impulse and angular impulse of the gravitational field jointly to the other material fields existing in nature, in the Riemann's effective spacetime, through its identity with Minkowski's pseudo Euclidean spacetime
The relativistic theory of gravitation beyond general relativity
No full textIt presents the basics of the “Relativistic theory of gravitation”, with the inclusion of original
texts, from various papers, published between 1987 and 2009, by theirs authors: S. S
Gershtein, A. A. Logunov, Yu. M. Loskutov and M. A. Mestvirishvili, additionally, together with
the introductions, summaries and conclusions of the author of this paper.
The “Relativistic theory of gravitation” is a gauge theory, compatible with the theories of
quantum physics of the electromagnetic, weak and strong forces, which defines gravity as the
fourth force existing in nature, as a static field equipped with the transmitter particles of the
virtual gravitons of spins 2 and 0, within the spirit of Galilei's principle of relativity, in his
generalization of Poincaré's Special Relativity that allowed the authors to universalize that the
physical laws of nature are complied with regardless of the frames of reference where they
apply, integrated into the Grossmann-Einstein Entwurf theory, in its further development, by
those authors, therefore, this theory preserves the conservation laws of energy-impulse and
angular impulse of the gravitational field jointly to the other material fields existing in nature,
in the Riemann's effective spacetime, through its identity with Minkowski's pseudo Euclidean
spacetime
The relativistic theory of gravitation beyond general relativity
No full textIt presents the basics of the “Relativistic theory of gravitation”, with the inclusion of original
texts, from various papers, published between 1987 and 2009, by theirs authors: S. S
Gershtein, A. A. Logunov, Yu. M. Loskutov and M. A. Mestvirishvili, additionally, together with
the introductions, summaries and conclusions of the author of this paper.
The “Relativistic theory of gravitation” is a gauge theory, compatible with the theories of
quantum physics of the electromagnetic, weak and strong forces, which defines gravity as the
fourth force existing in nature, as a static field equipped with the transmitter particles of the
virtual gravitons of spins 2 and 0, within the spirit of Galilei's principle of relativity, in his
generalization of Poincaré's Special Relativity that allowed the authors to universalize that the
physical laws of nature are complied with regardless of the frames of reference where they
apply, integrated into the Grossmann-Einstein Entwurf theory, in its further development, by
those authors, therefore, this theory preserves the conservation laws of energy-impulse and
angular impulse of the gravitational field jointly to the other material fields existing in nature,
in the Riemann's effective spacetime, through its identity with Minkowski's pseudo Euclidean
spacetime
The relativistic theory of gravitation beyond general relativity
No full textIt presents the basics of the “Relativistic theory of gravitation”, with the inclusion of original texts, from various papers, published between 1987 and 2009, by theirs authors: S. S Gershtein, A. A. Logunov, Yu. M. Loskutov and M. A. Mestvirishvili, additionally, together with the introductions, summaries and conclusions of the author of this paper.
The “Relativistic theory of gravitation” is a gauge theory, compatible with the theories of quantum physics of the electromagnetic, weak and strong forces, which defines gravity as the fourth force existing in nature, as a static field equipped with the transmitter particles of the virtual gravitons of spins 2 and 0, within the spirit of Galilei's principle of relativity, in his generalization of Poincaré's Special Relativity that allowed the authors to universalize that the physical laws of nature are complied with regardless of the frames of reference where they apply, integrated into the Grossmann-Einstein Entwurf theory, in its further development, by those authors, therefore, this theory preserves the conservation laws of energy-impulse and angular impulse of the gravitational field jointly to the other material fields existing in nature, in the Riemann's effective spacetime, through its identity with Minkowski's pseudo Euclidean spacetime
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