Targeting cancer cells overexpressing folate receptors with new terpolymer-based nanocapsules: Toward a novel targeted dna delivery system for cancer therapy

Chemotherapeutics represent the standard treatment for a wide range of cancers. However, these agents also affect healthy cells, thus leading to severe off-target effects. Given the non-selectivity of the commonly used drugs, any increase in the selective tumor tissue uptake would represent a significant improvement in cancer therapy. Recently, the use of gene therapy to completely remove the lesion and avoid the toxicity of chemotherapeutics has become a tendency in oncotherapy. Ideally, the genetic material must be safely transferred from the site of administration to the target cells, without involving healthy tissues. This can be achieved by encapsulating genes into non-viral carriers and modifying their surface with ligands with high selectivity and affinity for a relevant receptor on the target cells. Hence, in this work we evaluate the use of terpolymer-based nanocapsules for the targeted delivery of DNA toward cancer cells. The surface of the nanocapsules is decorated with folic acid to actively target the folate receptors overexpressed on a variety of cancer cells. The nanocapsules demonstrate a good ability of encapsulating and releasing DNA. Moreover, the presence of the targeting moieties on the surface of the nanocapsules favors cell uptake, opening up the possibility of more effective therapies

Reef Sediments Can Act As a Stony Coral Tissue Loss Disease Vector

Stony coral tissue loss disease (SCTLD) was first observed in 2014 near Virginia Key in Miami-Dade County, Florida. Field sampling, lab experiments, and modeling approaches have suggested that reef sediments may play a role in SCTLD transmission, though a positive link has not been tested experimentally. We conducted an ex situ transmission assay using a statistically-independent disease apparatus to test whether reef sediments can transmit SCTLD in the absence of direct contact between diseased and healthy coral tissue. We evaluated two methods of sediment inoculation: batch inoculation of sediments collected from southeast Florida using whole colonies of diseased Montastraea cavernosa, and individual inoculations of sediments following independent, secondary infections of similar to 5 cm(2) coral fragments. Healthy fragments of the coral species Orbicella faveolata and M. cavernosa were exposed to these diseased sediment treatments, as well as direct disease contact and healthy sediment controls. SCTLD transmission was observed for both batch and individual diseased sediment inoculation treatments, albeit with lower proportions of infected individuals as compared to disease contact controls. The time to onset of lesions was significantly different between species and among disease treatments, with the most striking infections occurring in the individual diseased sediment treatment in under 24 h. Following infection, tissue samples were confirmed for the presence of SCTLD signs via histological examination, and sediment subsamples were analyzed for microbial community variation between treatments, identifying 16 SCTLD indicator taxa in sediments associated with corals experiencing tissue loss. This study demonstrated that reef sediments can indeed transmit SCTLD through indirect exposure between diseased and healthy corals, and adds credence to the assertion that SCTLD transmission occurs via an infectious agent or agents. This study emphasizes the critical need to understand the roles that sediment microbial communities and coastal development activities may have on the persistence of SCTLD throughout the endemic zone, especially in the context of management and conservation strategies in Florida and the wider Caribbean

The Microchannel X-ray Telescope for the Gamma-Ray Burst mission SVOM

We present the Microchannel X-ray Telescope, a new light and compact focussing telescope that will be flying on the Sino-French SVOM mission dedicated to Gamma-Ray Burst science. The MXT design is based on the coupling of square pore micro-channel plates with a low noise pnCCD. MXT will provide an effective area of about 50 cmsq, and its point spread function is expected to be better than 3.7 arc min (FWHM) on axis. The estimated sensitivity is adequate to detect all the afterglows of the SVOM GRBs, and to localize them to better then 60 arc sec after five minutes of observation.Comment: 12 pages, 8 figures, to be published in SPIE Astronomical Telescopes + Instrumentation, Montreal, June 201

Semi-kinematic mount of the FIREBALL large optics

In the context of the NASA CNES FIREBALL balloon borne experiment, we present the design of a semi-kinematic mount to hold the 1 meter class mirrors of this mission. To maintain these large optics in a reasonable mass and price budgets we choose thin ULE mirrors with a thickness over diameter ratio of 1/16. Such thin mirrors require a multi support mount to reduce self weight deflection. Classical multi support mount used for ground based telescope would not survive the level of shock observed in a balloon experiment either at parachute opening or landing. To firmly maintain these mirrors in several points without noticeably deforming them we investigated the design of a two stages semi-kinematic mount composed of 24 monopods. We present the detailed design of this innovative mirror mount, the finite element modeling with the deduced optical wavefront deformation. During the FIREBALL integration and flight campaign in July 2007 at CSBF, we confirmed the validity of the mechanical concept by obtaining an image quality well within the required specifications. Variants of this approach are potentially applicable to large thin mirrors on ground-based observatories

Tetrazine-Triggered Release of Carboxylic-Acid-Containing Molecules for Activation of an Anti-inflammatory Drug.

In addition to its use for the study of biomolecules in living systems, bioorthogonal chemistry has emerged as a promising strategy to enable protein or drug activation in a spatially and temporally controlled manner. This study demonstrates the application of a bioorthogonal inverse electron-demand Diels-Alder (iEDDA) reaction to cleave trans-cyclooctene (TCO) and vinyl protecting groups from carboxylic acid-containing molecules. The tetrazine-mediated decaging reaction proceeded under biocompatible conditions with fast reaction kinetics (<2 min). The anti-inflammatory activity of ketoprofen was successfully reinstated after decaging of the nontoxic TCOprodrug in live macrophages. Overall, this work expands the scope of functional groups and the application of decaging reactions to a new class of drugs