Nuclear physics and astrophysics of the r-process

Some nuclear and astrophysical aspects of the r-process are discussed. Particular attention is paid to observations of abundances in metal-poor stars and their implications for the astrophysical site and yield patterns of the r-process. The effects of supernova neutrinos and related nuclear processes on the yield patterns are explored. The uncertainties in the theoretical nuclear input for the r-process are discussed and the need for experimental data is emphasized.Comment: 10 pages, 5 figures, Invited Talk at the International Nuclear Physics Conference (INPC2004

The Origin of the Heavy Elements: Recent Progress in the Understanding of the r-Process

There has been significant progress in the understanding of the r-process over the last ten years. The conditions required for this process have been examined in terms of the parameters for adiabatic expansion from high temperature and density. There have been many developments regarding core-collapse supernova and neutron star merger models of the r-process. Meteoritic data and observations of metal-poor stars have demonstrated the diversity of r-process sources. Stellar observations have also found some regularity in r-process abundance patterns and large dispersions in r-process abundances at low metallicities. This review summarizes the recent results from parametric studies, astrophysical models, and observational studies of the r-process. The interplay between nuclear physics and astrophysics is emphasized. Some suggestions for future theoretical, experimental, and observational studies of the r-process are given.Comment: typos in Eqs. (30) and (31) correcte

Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease that is refractory to medical intervention. Notch pathway antagonism has been shown to prevent pancreatic preneoplasia progression in mouse models, but potential benefits in the setting of an established PDA tumor have not been established. We demonstrate that the gamma secretase inhibitor MRK003 effectively inhibits intratumoral Notch signaling in the KPC mouse model of advanced PDA. Although MRK003 monotherapy fails to extend the lifespan of KPC mice, the combination of MRK003 with the chemotherapeutic gemcitabine prolongs survival. Combination treatment kills tumor endothelial cells and synergistically promotes widespread hypoxic necrosis. These results indicate that the paucivascular nature of PDA can be exploited as a therapeutic vulnerability, and the dual targeting of the tumor endothelium and neoplastic cells by gamma secretase inhibition constitutes a rationale for clinical translation

Safe approaches for camptothecin delivery: Structural analogues and nanomedicines

[EN] Twenty-(S)-camptothecin is a strongly cytotoxic molecule with excellent antitumor activity over a wide spectrum of human cancers. However, the direct formulation is limited by its poor water solubility, low plasmatic stability and severe toxicity, which currently limits its clinical use. As a consequence, two strategies have been developed in order to achieve safe and efficient delivery of camptothecin to target cells: structural analogues and nanomedicines. In this review, we summarize recent advances in the design, synthesis and development of camptothecin molecular derivatives and supramolecular vehicles, following a systematic classification according to structure-activity relationships (structural analogues) or chemical nature (nanomedicines). A series of organic, inorganic and hybrid materials are presented as nanoplatforms to overcome camptothecin restrictions in administration, biodistribution, pharmacokinetics and toxicity. Nanocarriers which respond to a variety of stimuli endogenously (e.g., pH, redox potential, enzyme activity) or exogenously (e.g., magnetic field, light, temperature, ultrasound) seem the best positioned therapeutic materials for optimal spatial and temporal control over drug release. The main goal of this review is to be used as a source of relevant literature for others interested in the field of camptothecin-based therapeutics. To this end, final remarks on the most important formulations currently under clinical trial are provided. (C) 2016 Elsevier B.V. All rights reserved.Financial support of the Spanish Ministry of Economy and Competitiveness (projects MAT2012-39290-C02-02 and SEV-2012-0267) is gratefully acknowledged. Dr. E.M. Rivero thanks the Cursol Foundation for a post-doctoral scholarship.Botella Asuncion, P.; Rivero-Buceta, EM. (2017). Safe approaches for camptothecin delivery: Structural analogues and nanomedicines. Journal of Controlled Release. 247:28-54. https://doi.org/10.1016/j.jconrel.2016.12.023S285424