Saturn Atmospheric Structure and Dynamics

2 Saturn inhabits a dynamical regime of rapidly rotating, internally heated atmospheres similar to Jupiter. Zonal winds have remained fairly steady since the time of Voyager except in the equatorial zone and slightly stronger winds occur at deeper levels. Eddies supply energy to the jets at a rate somewhat less than on Jupiter and mix potential vorticity near westward jets. Convective clouds exist preferentially in cyclonic shear regions as on Jupiter but also near jets, including major outbreaks near 35°S associated with Saturn electrostatic discharges, and in sporadic giant equatorial storms perhaps generated from frequent events at depth. The implied meridional circulation at and below the visible cloud tops consists of upwelling (downwelling) at cyclonic (anti-cyclonic) shear latitudes. Thermal winds decay upward above the clouds, implying a reversal of the circulation there. Warm-core vortices with associated cyclonic circulations exist at both poles, including surrounding thick high clouds at the south pole. Disequilibrium gas concentrations in the tropical upper troposphere imply rising motion there. The radiative-convective boundary and tropopause occur at higher pressure in the southern (summer) hemisphere due to greater penetration of solar heating there. A temperature “knee ” of warm air below the tropopause, perhaps due to haze heating, is stronger in the summer hemisphere as well. Saturn’s south polar stratosphere is warmer than predicted by radiative models and enhanced in ethane, suggesting subsidence-driven adiabatic warming there. Recent modeling advances suggest that shallow weather laye

A Fluorescent Probe to Measure DNA Damage and Repair

<div><p>DNA damage and repair is a fundamental process that plays an important role in cancer treatment. Base excision repair (BER) is a major repair pathway that often leads to drug resistance in DNA-targeted cancer chemotherapy. In order to measure BER, we have developed a near infrared (NIR) fluorescent probe. This probe binds to a key intermediate, termed apurinic/apyrimidinic (AP) site, in the BER pathway where DNA damage and repair occurs. We have developed an assay to show the efficacy of the probe binding to AP sites and have shown that it can distinguish AP sites in DNA extract from chemotherapy treated cells. This probe has potential application in monitoring patient response to chemotherapy and evaluating new drugs in development.</p></div

Gold Nanoparticle-Based Fluorescent Theranostics for Real-Time Image-Guided Assessment of DNA Damage and Repair

Chemotherapeutic dosing, is largely based on the tolerance levels of toxicity today. Molecular imaging strategies can be leveraged to quantify DNA cytotoxicity and thereby serve as a theranostic tool to improve the efficacy of treatments. Methoxyamine-modified cyanine-7 (Cy7MX) is a molecular probe which binds to apurinic/apyrimidinic (AP)-sites, inhibiting DNA-repair mechanisms implicated by cytotoxic chemotherapies. Herein, we loaded (Cy7MX) onto polyethylene glycol-coated gold nanoparticles (AuNP) to selectively and stably deliver the molecular probe intravenously to tumors. We optimized the properties of Cy7MX-loaded AuNPs using optical spectroscopy and tested the delivery mechanism and binding affinity using the DLD1 colon cancer cell line in vitro. A 10:1 ratio of Cy7MX-AuNPs demonstrated a strong AP site-specific binding and the cumulative release profile demonstrated 97% release within 12 min from a polar to a nonpolar environment. We further demonstrated targeted delivery using imaging and biodistribution studies in vivo in an xenografted mouse model. This work lays a foundation for the development of real-time molecular imaging techniques that are poised to yield quantitative measures of the efficacy and temporal profile of cytotoxic chemotherapies

SSB activity assay comparison of ARP, MX, and 7.

<p>(A) ARP (1 nmol), MX (1 nmol), and <b>7</b> (1 nmol) with UDG (5 units) and U:A DNA (5pmol) as a function of incubation time prior to APE (10 units) addition. (B) ARP (200 nmol), MX (200 nmol), and <b>7</b> (2 nmol) with UDG (5 units) and U:A DNA (5 pmol) as a function of incubation time prior to APE (1 unit) addition.</p

Evaluation of base pairing on SSB activity.

<p>Time course represents incubation time of U:X DNA before APE addition with UDG and (A) compound <b>7</b> or (B) with vehicle control.</p

Time course of 7 binding to calf thymus AP DNA.

<p>Time course of 7 binding to calf thymus AP DNA.</p

Synthesis of NIR probe 7.

<p>Reagents and conditions: a) <i>N</i>-Boc hydroxylamine, DBU, DCM, r.t., 68%; b) hydrazine monohydrate, MeOH, r.t., 88%; c) 4-hydroxyphenylacetic acid, EDC·HCl, HOBt·H₂O, DMF, r.t. 80%; d) 5, NaH, DMF, r.t. 55%; and e) TFA, DCM, r.t. 71%.</p

Competition studies between 7 and MX or ARP in genomic DNA.

<p>(A) MX or (B) ARP for AP sites in calf thymus DNA treated with heat and acid for 45 min are shown. The molar ratio of probe to <b>7</b> was increased by increasing [probe] and maintaining a constant [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131330#pone.0131330.ref007" target="_blank">7</a>]. ED₅₀ values were calculated from the fittings to be 2600-fold excess for ARP and 3000-fold excess for MX.</p

Dose-response of 7 in calf thymus AP DNA.

<p>Dose-response of 7 in calf thymus AP DNA.</p