Coupled zircon U-Pb age, trace-element, and Lu-Hf isotope analyses from central Sierra Nevada (eastern California, USA) metavolcanic strata reveal the expression of three Mesozoic arc flare-ups in the volcanic record over ∼150 m.y. of magmatic activity. Zircon εHf(i) values vary up to 20 epsilon units within individual samples and coeval sample populations but show no clear links with other geochemical indices, requiring both mixing and fractionation for arc magma genesis. Zircon compositions show repeated temporal trends across flare-ups: Hf isotopes spanning evolved to juvenile values converge to more juvenile compositions, middle rare earth element (MREE) depletion and heavy REE slopes increase during flare-up main phases, and highly variable U/Yb values converge to low values as flare-ups conclude. Despite pervasive contamination, juvenile source magmas dominate magmas erupted throughout the entirety of high-magma-addition episodes. Arc flare-ups thus represent ∼30 m.y. of increased mantle magma input that represents significant continental crust formation in Cordilleran arcs.
Targeted
delivery of chemotherapeutics to tumors has the potential
to reach a high dose at the tumor while minimizing systemic exposure.
Incorporation of antibody within a micellar platform represents a
drug delivery system for tumor-targeted delivery of antitumor agents.
Such modified immunomicelles can result in an increased accumulation
of antitumor agents and enhanced cytotoxicity toward cancer cells.
Here, mixed dendrimer micelles (MDM) composed of PEG2k-DOPE-conjugated
generation 4 polyamidoamine dendrimer G4-PAMAM-PEG2k-DOPE
and PEG5k-DOPE were coloaded with doxorubicin and siMDR-1.
This formulation was further modified with monoclonal antibodies 2C5
with nucleosome-restricted specificity that effectively recognized
cancer cells via the cell-surface-bound nucleosomes. Micelles with
attached 2C5 antibodies significantly enhanced cellular association
and tumor killing in both monolayer and spheroid tumor models as well
as in vivo in experimental animals compared to the
nontargeted formulations.
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